JP6069287B2 - Self-injection device - Google Patents

Description

  The present invention generally relates to a substance delivery device that is more convenient for the patient and easier to use and efficient. Furthermore, the present invention generally relates to patch-like self-contained substance infusion devices or self-injection devices that can be used to deliver a variety of substances or agents to a patient. More particularly, the present invention relates to a patch-like infusion device or self-injection device having an end-of-dose indicator.

  A vast number of people, such as those suffering from illnesses such as diabetes, utilize some form of infusion therapy, such as daily infusions of insulin to maintain tight control of glucose levels. Currently, in the example of an insulin infusion device, there are two main daily insulin treatment modes. The first mode includes a syringe and an insulin pen. These devices are simple to use and relatively inexpensive, but typically require a needle to be punctured every 3 to 4 injections per day. The second mode includes infusion pump therapy, which requires the purchase of an expensive pump that lasts about 3 years. The high cost of this pump (approximately 8 to 10 times the daily cost of syringe treatment) and its limited lifespan are major obstacles to this type of treatment. Insulin pumps are a relatively old technology and are cumbersome to use. In addition, from a lifestyle perspective, it is extremely inconvenient to place a tube (known as an “infusion set”) that connects the pump to the delivery site of the patient's abdomen, and the pump is relatively heavy and therefore portable Is a burden. However, from the patient's point of view, the overwhelming majority of patients who have used a pump prefer to keep using the pump all the time. This is because infusion pumps are more complex than syringes and pens, but have the advantage that insulin can be infused continuously, doses are accurate, and delivery schedules are programmable. Thereby, glucose is more tightly controlled and health is felt improved.

  There is a growing interest in better therapies, so pump treatment has grown visibly and the number of daily injections has increased. What is required to fully meet this growing interest in these and similar infusion examples is the best features of daily injection therapy (low cost and ease of use) and the best features of insulin pumps. (Continuous infusion and precise dose), combined with insulin, is a form of insulin delivery or infusion that avoids the respective drawbacks.

  Several attempts have been made to provide portable or “wearable” drug infusion devices that are inexpensive and easy to use. Some of these devices are intended to be partially or wholly disposable. Theoretically, this type of device can provide many of the benefits of an infusion pump without the associated costs and inconveniences. Unfortunately, however, many of these devices suffer from patient pain (depending on the gauge and / or length of the needle used), compatibility between the substance being delivered and the materials used to construct the infusion device, and interaction with each other. As well as the disadvantages that the patient may not function properly if not operated correctly (eg, an “invasion” injection due to the device operating too early). In particular, when using short and / or thin gauge needles, manufacturing difficulties and difficulties in controlling the penetration depth of the needle are also encountered. The possibility of injury from needle sticks of people touching used devices is also a problem.

US Pat. No. 6,569,143 International Publication No. 02/083214 Pamphlet

Biochem Biophys Acta, 1989, 67, 1007 Rubins et al., Microbial Pathogenesis, 25, 337-342

  Accordingly, there is a need for an alternative to current infusion devices such as insulin infusion pumps that are simpler to manufacture and have improved usage in insulin and non-insulin applications.

  One aspect of the present invention is a patch-like infusion device that can be conveniently worn by pressing against the skin and can inject the desired substance using one or more microneedles to minimize pain. It is to provide a self-injection device. A further aspect of the present invention is to provide such an infusion device or self-injection device having a dose end indicator.

  The above and / or other aspects of the present invention include a body having a reservoir that can contain a drug disposed therein, an injection needle that pierces the skin of a patient and has a lumen and communicates with the reservoir. This is accomplished by providing a device that delivers a drug into the patient's body by injection into or through the patient's skin, including a needle and a pressurizing system that pressurizes the reservoir. The device further includes indicator means visible from outside the device to indicate that the delivery of the drug has been substantially completed.

  The above and / or other aspects of the present invention further include a main body, a liquid reservoir capable of containing a drug disposed within the main body, a syringe needle for administering the drug from the puncture liquid reservoir through the patient's skin, and a pressure reservoir. This is accomplished by providing a device that delivers a drug into the patient's body by injection into or through the patient's skin, including a pressurized system. The device further includes an end-of-dose indicator that is visible from outside the device and indicates that the delivery of the drug is substantially complete.

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

  These and / or other aspects and advantages of the present invention will be more readily understood upon reading the following more detailed description in conjunction with the accompanying drawings.

1 is a perspective view of one embodiment of a patch-like infusion device or self-injection device in a pre-actuated state prior to actuation. FIG. FIG. 2 is a partially exploded view of the injection device of FIG. 1 in a pre-operation state. FIG. 2 is a partially exploded view of the infusion device of FIG. 1 in a pre-actuated state with the actuating button rotated outward as can be seen in more detail. FIG. 2 is a fully exploded view of the injection device of FIG. 1 in a pre-operational state. FIG. 2 is a cross-sectional view of the injection device of FIG. 1 in a pre-operation state. FIG. 2 is a cross-sectional view of the injection device of FIG. FIG. 2 is a partially exploded view of the injection device of FIG. 1 with a safety mechanism installed. FIG. 2 is a partially exploded view of the injection device of FIG. 1 after operation. FIG. 2 is a fully exploded view of the injection device of FIG. 1 after operation. FIG. 2 is a cross-sectional view of the injection device of FIG. 1 after operation. FIG. 2 is a partially exploded view of the injection device of FIG. 1 after deployment of the safety mechanism. FIG. 2 is a cross-sectional view of the injection device of FIG. 1 after deployment of the safety mechanism. It is a bottom view of a safety mechanism. It is another figure of the structure of a safety mechanism. FIG. 2 is a dose end indicator and its operation in the infusion device of FIG. 1. FIG. 2 is a dose end indicator and its operation in the infusion device of FIG. 1. FIG. 2 is a dose end indicator and its operation in the infusion device of FIG. 1. FIG. 2 is a dose end indicator and its operation in the infusion device of FIG. 1. FIG. 6 is a diagram of another dose end indicator and its operation in the infusion device of FIG. 1. FIG. 6 is a diagram of another dose end indicator and its operation in the infusion device of FIG. 1. FIG. 10 is a diagram of yet another dose end indicator. FIG. 10 is a diagram of yet another dose end indicator. FIG. 17B is a view of the dose end indicator of FIG. 17A located in the infusion device of FIG. FIG. 10 is a diagram of yet another dose end indicator and its operation. FIG. 10 is a diagram of yet another dose end indicator and its operation. FIG. 19B is a diagram of the operation of the dose end indicator of FIG. 19A in the infusion device of FIG. FIG. 19B is a diagram of the operation of the dose end indicator of FIG. 19A in the infusion device of FIG. FIG. 10 is a diagram of yet another dose end indicator and its operation. FIG. 10 is a diagram of yet another dose end indicator and its operation. FIG. 21B is a diagram of the operation of the dose end indicator of FIG. 21A in the infusion device of FIG. FIG. 21B is a diagram of the operation of the dose end indicator of FIG. 21A in the infusion device of FIG. FIG. 6 is an illustration of an embodiment of a marker showing progress of drug delivery. FIG. 6 is an illustration of an embodiment of a marker showing progress of drug delivery. FIG. 6 is an illustration of an embodiment of a marker showing progress of drug delivery. FIG. 10 is a diagram of yet another dose end indicator and its operation. FIG. 10 is a diagram of yet another dose end indicator and its operation. FIG. 24B is a diagram of the operation of the dose end indicator of FIG. 24A in the infusion device of FIG. FIG. 24B is a diagram of the operation of the dose end indicator of FIG. 24A in the infusion device of FIG. FIG. 6 is a diagram of another dose end indicator and its operation. FIG. 6 is a diagram of another dose end indicator and its operation. FIG. 26B is a diagram of the operation of the dose end indicator of FIG. 26A in the infusion device of FIG. FIG. 26B is a diagram of the operation of the dose end indicator of FIG. 26A in the infusion device of FIG. 1 is an embodiment of an injection device having an injection port. FIG.

  Reference will now be made in detail to the embodiments of the present invention. Examples of embodiments are illustrated in the accompanying drawings. Like reference numerals refer to like elements throughout the drawings. The described embodiments illustrate the invention with reference to the drawings.

  The embodiments of the invention described below are used as a convenient patch-like infusion device or self-injection device 100 that delivers a pre-measured dose of a substance such as a liquid drug or drug to a patient over a period of time or at a time. be able to. The device is preferably provided to the user in a pre-filled state, i.e. a drug or drug already in the reservoir of the device. The patch-like infusion device or self-injection device 100 described herein (eg, as shown in FIG. 1) can be used by a patient and / or caregiver, but for convenience, hereinafter, the device user is referred to as a “patient”. Called. Further, for convenience, terms such as “vertical” and “horizontal” or “top” and “bottom” are used to denote relative directions with respect to the injection device 100 positioned in a horizontal plane. However, it will be understood that the injection device 100 is not limited to such an orientation and can be used in any orientation. Furthermore, the choice and use of either the term “injection device” or “self-injection device” to describe a device embodying the invention is not meant to narrow. An infusion device without a self-injection function also falls within the scope of the present invention as a self-injection device that does not perform continuous infusion. For convenience, but not for purposes of limitation, the term “injection device” will be used in the following description.

  The patch-like infusion device 100 of FIG. 1 is self-contained and is attached to the patient's skin surface by an adhesive placed on the bottom surface of the infusion device 100 (as described in more detail below). Once properly positioned and actuated by the patient, one or more patient needles (e.g., microscopic) are passed through the needle manifold using the spring pressure released on the flexible reservoir in the device. The contents of the liquid reservoir can be emptied by the needle). The substance in the reservoir is then delivered through the patient's skin by a microneedle that is pierced into the skin. It will be appreciated that other embodiments are possible using different types of energy storage devices instead of springs, which may be mechanical, electrical and / or chemical in nature.

  As will be apparent to those skilled in the art, there are many ways to construct and use the patch-like infusion device 100 disclosed herein. Reference is made to the embodiments illustrated in the drawings and the following description, however, the embodiments disclosed herein are not exhaustive of the various alternative designs and embodiments encompassed by the invention disclosed herein. In each of the embodiments disclosed herein, the device refers to an infusion device, but it is also possible to inject a substance at a much faster (single dose) rate than is generally achieved by a typical infusion device. it can. For example, the contents can be delivered in as little as a few seconds or as long as a few days.

  In the device embodiment shown in FIGS. 1-12, a push-button patch-like infusion device 100 is shown in which operation and energization of the device is performed in a single multi-function / step process. FIG. 1 shows an assembled embodiment of the injection device 100 in a pre-actuated state. 2-6 show a partially exploded cross-sectional view of the injection device 100 in a pre-operation state. FIG. 7 shows a partially exploded view of the injection device 100 with the safety mechanism installed. 8-10 show an exploded cross-sectional view of the injection device 100 after operation. 11 and 12 show an exploded cross-sectional view of the injection device 100 after the safety mechanism has been deployed. The infusion device 100 is in a pre-actuated state (eg, as shown in FIGS. 1, 2 and 5), an operational or starting state (eg as shown in FIGS. Configured to operate between.

  As shown in FIG. 1, an embodiment of the patch-like infusion device 100 includes a bottom enclosure 104, a safety mechanism 108, a flexible needle cover 112, a top enclosure 116, a reservoir subassembly 120, a dose end indicator (EDI) 124. , And an activation button 128 that includes a patient interface 132. 2-6, the injection device 100 further includes a rotor or actuating ring 136, a pressure spring 140, a dome-like metal plunger 144 and a drive spring 148.

  The flexible needle cover 112 provides safety to the patient and the device by protecting at least one needle 152 (described in more detail below) and providing a sterility barrier. Needle cover 112 protects needle 152 during device manufacture, protects the patient prior to use, and provides a sterility barrier at any point prior to removal. According to one embodiment, the needle cover 112 is attached by press fitting with a needle manifold having at least one needle 152 disposed therein. Further, according to one embodiment, the needle opening 156 (described in more detail below) of the safety mechanism 108 is shaped to closely correlate with the outer periphery of the needle cover 112.

For example, as shown in FIGS. 2, 3, 5, 6, 8, 10, 12, the reservoir subassembly 120 includes a reservoir 160, a reservoir dome seal 164, a valve 168, at least one needle 152, and a valve 168. And at least one groove or channel 174 in channel arm 172 that is disposed between needle 152 and creates a flow path therebetween (see, eg, FIGS. 2 and 8). Liquid reservoir 160 includes a dome 176. In addition, the reservoir subassembly 120 includes a removable needle cover 112 that selectively covers at least one needle 152. According to one embodiment, the reservoir subassembly 120 further includes a reservoir arm seal 180 that covers the channel arm 172. Preferably, the needle 152 includes a needle manifold and a plurality of microneedles 152.

  For example, as shown in FIG. 5, a reservoir dome seal (flexible film) 164 of the reservoir subassembly 120 is disposed between the plunger 144 and the dome 176. The contents of the reservoir (eg, medical material) of the infusion device 100 are placed in the space between the reservoir dome seal 164 and the dome 176. The sump 160 is defined by combining the sump dome seal 164, the dome 176 and the space between them. The dome 176 is preferably transparent so that the contents of the sump can be seen. The sump dome seal 164 can be made of a non-stretchable material or laminate, such as a metal-coated film or other similar material. For example, one possible flexible laminated film that can be used for the reservoir dome seal 164 is a first chemical layer, a second chemical layer known to those skilled in the art that provides an attachment mechanism to the third metal layer, A third metal layer selected based on the barrier characteristics and a fourth layer comprising polyester and / or nylon are included. By using a metal coated film or a metallized film in conjunction with a rigid portion (eg, dome 176), the barrier properties of the sump 160 are improved, thereby increasing the shelf life of the contents contained in the sump. Will be extended or improved. For example, when the contents of the reservoir contain insulin, the main material of the contact portion of the reservoir 160 is linear low density polyethylene (LLDPE), low density polyethylene (LDPE), cyclic olefin copolymer (COC) and Teflon. (Registered trademark). As will be explained in more detail below, the main materials of contact with the contents of the sump in the remaining channels are COC and LLDPE, as well as thermoplastic elastomer (TPE), medical acrylic, stainless steel, needles An adhesive (for example, UV-curing adhesive) can be further included. Such materials that remain in contact with the contents of sump 160 for extended periods of time preferably pass ISO 10-993 and other applicable biological compatibility tests.

  The sump subassembly 120 can be stored for a predetermined shelf life of the contents of the sump in the relevant controlled environment without adversely affecting the contents and can be applicable to various environmental conditions. Further preferred. Furthermore, a barrier that prevents gas, liquid, and / or solid material from entering or exiting the contents at a faster rate than acceptable to meet the desired storage period may be a component of the sump subassembly 120. Provided. In the embodiment described above, the reservoir material can be stored and operated in a temperature range of about 34 degrees Fahrenheit (1 ° C.) to about 120 degrees Fahrenheit (49 ° C.), and the storage period should be 2 years or more. Can do.

  In addition to meeting stability requirements, the reservoir subassembly 120 performs its operation by passing any number of leak tests, such as holding the sample at 30 psi (21 g / mm 2) for 20 minutes without leaking. Further guarantees can be made. Furthermore, the additional benefits of filling, storage and delivery due to the reservoir configuration include minimization of headspace and suitability as described in more detail below.

  In one embodiment, reservoir 160 is emptied prior to filling. By emptying the reservoir 160 prior to filling so that the dome 176 has only a slight depression, the top space and excessive waste within the reservoir 160 can be minimized. Furthermore, the shape of the sump can be configured to match the type of biasing mechanism (eg, pressure spring 140 and plunger 144). Furthermore, the use of a flexible reservoir 160 that is emptied during filling minimizes any air or bubbles in the filled reservoir 160. The use of a flexible reservoir 160 is also extremely beneficial when the infusion device 100 is subject to external pressure or temperature fluctuations, which can increase the internal pressure of the reservoir. In such a case, the flexible reservoir 160 expands and contracts with the contents of the reservoir, thereby eliminating leakage caused by the expansion and contraction force.

  Yet another feature of the reservoir 160 is that it can be examined for particulates either automatically during filling or by the patient during use. One or more reservoir barriers, such as the dome 176, can be molded from a clear, clear plastic material, thereby allowing inspection of the material in the reservoir. A clear, clear plastic material is preferably a cyclic olefin copolymer, characterized by high clarity and clarity, low extract, and biological compatibility with the material contained in the reservoir 160. Suitable materials include Luisville, KY's Zeon Chemicals, L .; P. Commercially available under the name “BD CCP Resin” S. Listed in Food and Drug Administration and DMF16368. In such applications, the shape of the reservoir 160 that can interfere with the inspection is minimized (ie, can be rotated during the inspection).

Channel arm 172 is provided in the form of at least one flexible arcuate arm that extends from valve 168 to needle manifold or microneedle 152. The arcuate arm has a groove 174 (see, for example, FIG. 2) formed therein. A reservoir arm seal 180 covers the groove 174 and provides a fluid flow path between the valve 168 and the needle manifold or microneedle 152. The fluid flow path between the reservoir 160 and the microneedles 152 (for example, disposed in the channel arm 172 shown in FIG. 8) is made of a material similar to or the same as the material of the reservoir 160 described above. For example, the channel arm 172 can be made of the same material as the dome 176 and the reservoir arm seal 180 can be made of the same material as the reservoir dome seal 164. According to one embodiment, both channel arms 172 can be used as a fluid flow path between the valve 168 and the needle manifold or microneedle 152. According to other embodiments, only one of the channel arms 172 is used as a fluid flow path and the remaining channel arms 172 provide structural support. In such embodiments, the groove 174 extends entirely from the valve 168 to the needle manifold or microneedle 152 only in the channel arm 172 to be used as a fluid flow path.

The channel arm 172 needs to be flexible enough to withstand the force of actuation. 2 and FIG. 8 in comparison with each other, the position of the channel arm 172 is compared (in FIG. 2, it is covered by the reservoir arm seal 180. For clarity, the reservoir arm seal 180 is removed in FIG. The channel arm 172 elastically deforms when the microneedle 152 is stabbed into the patient's skin (this is described in more detail below). During such deformation, the channel arm 172 must maintain the integrity of the fluid flow path between the valve 168 and the needle manifold or microneedle 152. Furthermore, the material of the channel arm 172 is compatible with a number of biological compatibility and storage tests. For example, as shown in Table 1 below, when the infusion device contains insulin, the main materials for the contact in the reservoir 160 are linear low density polyethylene, cyclic olefin copolymer (COC) and Teflon (registered trademark). ) And can further include a clear clear plastic. The main material of the contact in the remaining flow path between the sump 160 and the needle needle microneedles 152 includes COC and / or medical acrylic, LLDPE, TPE, stainless steel, and needle adhesive.

  More specifically, the microneedles 152 can be constructed of stainless steel and the needle manifold can be constructed of polyethylene and / or medical acrylic. Such materials preferably pass the biological compatibility test of ISO 10-993 when in contact with the contents of the sump for an extended period of time.

A valve 168 disposed between the sump 160 and the channel arm 172 selectively permits and restricts fluid flow therebetween. The valve 168 moves between a pre-actuated position (eg, shown in FIGS. 2, 3, 6) and an actuated position (eg, shown in FIGS. 8-10). When in the activated position, the valve allows fluid flow between the reservoir 160 and the channel arm 172, and thus fluid flow to the needle manifold and microneedle 152.

In use, the valve 168 is ultimately pushed to the activated position by movement of the activation button 128. This is best illustrated by the movement of valve 168 between FIGS. As shown in FIG. 10, movement of valve 168 advances the distal end of expanded valve 168, which causes drug to flow from reservoir 160 to channel arm 172 and through the fluid flow path to the down needle manifold. It will be able to flow.

  The above-described embodiments include at least one needle 152 or microneedle 152, but may include several, for example, two illustrated microneedles 152. Each microneedle 152 is preferably at least 31 gauge or less, such as 34 gauge, and is secured within a patient needle manifold that may be placed in fluid communication with the reservoir 160. When two or more microneedles 152 are included in the injection device 100, they can be of different lengths, different gauges, or a combination of different lengths and gauges along the length of the body. One or more ports may be included, preferably disposed near the tip of the microneedle 152 or in the vicinity of any of the microneedles 152 having a tip chamfer.

  According to one embodiment, the gauge of microneedle 152 determines the delivery rate of the contents of the reservoir of infusion device 100. Delivering the contents of a reservoir using a 34 gauge microneedle 152 for longer infusions than is generally associated with direct injection with a syringe that requires a much larger cannula or needle Is practical. In the disclosed embodiment, any microneedle 152 intended for either intracutaneous or subcutaneous space can be used, but the exemplary embodiment is for skins between 1 mm and 7 mm in length (ie, 4 mm) An inner microneedle 152 is included. The arrangement of microneedles 152 may be a linear or non-linear array and may include any number of microneedles 152 as required for a particular application.

As described above, the microneedles 152 are positioned within the needle manifold. The needle manifold is provided with at least one fluid communication path for each microneedle 152. The manifold can simply provide a single path for one or more microneedles 152, or it can include multiple fluid paths or channels that individually deliver the contents of the reservoir to each microneedle 152. . These paths or channels can further include a serpentine path for moving the contents. This serpentine path acts as a fluid flow restriction and flow rate affecting flow restriction. The channel or path within the needle manifold can vary in width, depth and configuration depending on the application, and the channel width typically ranges from about 0.015 inch (0.38 mm) to about 0.04 inch ( 1.02 mm), preferably 0.02 inches (0.51 mm), and is configured to minimize voids in the manifold.

  According to one embodiment, the reservoir subassembly 120 has a pair of holes 184, 188 that assist in aligning the reservoir subassembly 120 with respect to the bottom enclosure 104. A first post 192 and a second post 196 (described in more detail below) of the bottom enclosure 104 are inserted through respective holes 184, 188.

  4, 7, 9, with the sump subassembly 120 removed, the bottom enclosure 104 includes a substantially cylindrical housing 200 in which a pressure spring 140 and a plunger 144 are disposed. It is shown that. According to one embodiment, the cylindrical housing 200 includes a plurality of recessed channels 204. The recessed channel 204 guides the respective plurality of legs 208 and end 212 of the plunger 144 as the plunger 144 moves within the housing 200. The leg 208 forms a plunger tab 214 with the end 212. As shown in FIGS. 4, 7, and 9, for example, the recessed channel 204 extends only partway down from the top of the cylindrical housing 200. Below the recessed channel 204 is an opening 216 through which the distal end 212 of the plunger 144 can extend out of the cylindrical housing 200. The opening 216 is substantially L-shaped and has a horizontal portion at the base of the cylindrical housing 200 and a vertical portion that is substantially aligned with the recessed channel 204.

  When the injection device 100 is in a pre-actuated state, the pressure spring 140 is compressed by the plunger 144 (eg, as shown in FIGS. 4-6), and the distal end 212 of the plunger 144 is substantially open. 216 is disposed within the horizontal portion. The force of the pressure spring 140 biases the distal end 212 of the plunger 144 against the top of the horizontal portion of the opening 216 (ie, the ledge of the cylindrical housing 200). As will be described in more detail below, the pressure spring 140, in combination with the plunger 144, forms a pressure system that pressurizes the reservoir 160 when the infusion device 100 is actuated.

  As will be described in more detail below, the rotor 136 is disposed about the base of the cylindrical housing 200 between a pre-operation position (eg, as shown in FIGS. 2-4) and an operation position (eg, as shown in FIGS. 8-10). Rotate. As rotor 136 rotates from a pre-actuated position to an actuated position, surface 220 that engages at least one end of rotor 136 (eg, as shown in FIG. 4) engages at least one of end 212 of plunger 144. The plunger 144 is rotated so that the end 212 is aligned with the vertical portion of the opening 216 and the recessed channel 204. At this point, the pressure spring 140 moves the plunger 144 upward, with the end 212 guided by the raised channel 204.

  The pressure spring 140 is included in the injection device 100 and applies an essentially uniform force to the liquid reservoir 160 to push out the contents from the liquid reservoir 160. The pressure spring 140 is used to store energy that pressurizes the liquid reservoir 160 when released in use. The pressure spring 140 is held in a compressed state by engagement between the distal end portion 212 of the plunger 144 and the cylindrical housing 200. This engagement prevents the pressure spring 140 from stressing the reservoir 160 film (described below) or any remaining device components (other than the bottom enclosure 104 and plunger 144) during storage. Become. Plunger 144 is sufficiently rigid to withstand spring tension and deformation and should not break under normal loads.

As described above, when the rotor 136 rotates from the pre-actuated position to the actuated position, the rotor 136 engages at least one of the distal ends 212 of the plunger 144 and rotates the plunger 144 so that the distal end 212 is perpendicular to the opening 216. Align with part and recessed channel 204. The compressed pressure spring 140 then moves the plunger upward, thereby applying a force on the film in the reservoir 160. The pressure spring 140 is preferably within the reservoir 160 from about 1 psi (0.7 g / mm 2) to about 50 psi (35 g / mm 2), more preferably from about 2 psi (1.4 g / mm 2) to about 25 psi (17. A pressure of 5 g / mm2) can be generated and the contents of the reservoir can be delivered intradermally. In the case of subcutaneous injection or infusion, about 2 psi (1.4 g / mm 2) to about 5 psi (3.5 g / mm 2) will be sufficient.

  According to one embodiment, the activation button 128 includes a patient interface 132 that the patient presses to activate the infusion device 100. Actuation button 128 further includes a hinge arm 224 and an actuation arm 228 (eg, both shown in FIG. 3). The hinge arm 224 of the activation button 128 includes a cylindrical portion with an opening. Actuating arm 228 includes a tab 230 (see, eg, FIG. 3). According to one embodiment, the tab 230 includes a bearing surface 232 and a locking surface 234 disposed adjacent to the cantilevered end of the bearing surface 232. According to one embodiment, the tab 230 forms an acute angle with respect to the main portion of the actuation arm 228.

  A first post 192 disposed on the bottom enclosure 104 extends upward from the bottom enclosure 104. According to one embodiment (eg, as shown in FIGS. 4 and 7), the base of the first post 192 includes a pair of flat sides 236 and a pair of rounded sides 240. Further, as shown, for example, in FIGS. 4 and 7, the second post 196, the first drive spring base 244 and the second drive spring base 248 extend upward from the bottom enclosure 104. As will be described in more detail below, a first drive spring base 244 and a second drive spring base 248 secure each end of the drive spring 148. The base 244 of the first drive spring is disposed adjacent to the second post 196 and spaced from the second post 196.

  According to one embodiment, FIGS. 3 and 6 illustrate positioning the activation button 128 relative to the bottom closure 104 for assembly of the activation button 128. In this position, the opening in the cylindrical portion of the hinge arm 224 allows the actuation button 128 to slide horizontally (through the flat side 236) into engagement with the first post 192. The hinge arm 224 (and thus the activation button 128) can then be rotated around the first post 192. When the actuating arm 228 enters the space between the second post 196 and the first drive spring base 244, the cantilevered end of the bearing surface 232 of the tab 230 depresses the retaining surface 252 of the second post 196. Until passing, at least one of the tab 230 and the actuation arm 228 is elastically deformed. The audible click sound is caused by the movement of the cantilevered end of the bearing surface 232 of the tab 230 through the retaining surface 252 (see, eg, FIG. 4) and the engagement between the locking surface 234 and the retaining surface 252 of the tab 230. And tactile feedback is provided to communicate that the activation button 128 is in the pre-actuated position.

  Referring back to FIGS. 2-4 and FIGS. 7-9, the rotor 136 further includes an actuation protrusion 256 and a drive spring holder 260. The actuating arm 228 of the actuating button 128 engages the actuating protrusion 256 when the patient depresses the actuating button 128, thereby rotating the rotor 136 from the pre-actuated position to the actuated position.

  The drive spring holder 260 maintains the drive spring 148 in the pre-operation position when the rotor 136 is in the pre-operation position. As described above, the first drive spring base 244 and the second drive spring base 248 secure both ends of the drive spring 148. Approximately in the middle of the drive spring 148 is a substantially U-shaped protrusion for engaging a drive spring holder 260 of the rotor 136, as shown, for example, in FIGS. Thus, when the rotor 136 is in the pre-operation position and the drive spring 148 is engaged with the drive spring holder 260, the drive spring 148 is maintained in tension. When the drive spring holder 260 releases the drive spring 148 (that is, when the rotor rotates from the pre-operation position to the operation position, for example, as shown in FIGS. 8 to 10), the drive needle 148 causes the microneedles 152 to move to the bottom enclosure 104. It extends out of the injection device 100 through the opening 300 (and the opening of the safety mechanism 108 described in more detail below).

Thus, as will be described in more detail below, actuation and biasing of the infusion device 100 performed in a single multifunctional / step process will cause the patient to depress the actuation button 128 and the actuation arm 228 of the actuation button 128. Rotation of the rotor 136 by engagement of the operating projection 256 of the rotor 136 is included. As described above, rotation of the rotor 136 rotates and releases the plunger 144, thereby pressurizing the fluid in the reservoir 160. Furthermore, rotation of the rotor 136 releases the drive spring 148 from the drive spring holder 260, thereby moving the microneedle 152 and extending it out of the injection device 100. The single multi-function / step process further includes movement of the valve 168 from a pre-actuated position to an actuated position by engaging and moving the actuating button 128 when the actuating button 128 is depressed. This initiates fluid flow through the channel arm 172 between the reservoir and the microneedle 152.

  As described above, the patch-like injection device 100 further includes a safety mechanism 108. A locking needle safety mechanism 108 is provided to prevent damage from unintentional or accidental needle sticks, prevent intentional reuse of the device, and shield exposed needles. Safety mechanism 108 is automatically activated immediately after removal of infusion device 100 from the patient's skin surface. According to one embodiment described in more detail below, the flexible adhesive pad 264 adheres to the bottom portion of the bottom enclosure 104 and the bottom portion of the safety mechanism 108. The adhesive pad 264 contacts the patient's skin during use and holds the infusion device 100 in place on the skin surface. For example, as shown in FIGS. 11 and 12, when the injection device 100 is removed from the skin surface, the safety mechanism 108 extends to a position where the microneedle 152 is shielded. When fully extended, the safety mechanism locks into place, thereby preventing accidental injury or exposure to the patient needle 152.

  In general, a passive safety system is most desirable. This allows the device to be protected by itself if it is accidentally removed or if the patient forgets that there is a safety step. One typical use of this infusion device 100 is to supply human growth hormone, which is usually done at night, so that a patient (such as a child) wearing the device can deliver as long as 10 minutes. Even if you do n’t expect it, you ’re actually expected to wear it all night. If the infusion device 100 without a passive system is removed, the microneedle 152 may pierce the patient or caregiver again. This solution either limits the activity in use or includes a passive safety system.

  There are generally three options for safety systems. The first option is to retract the needle 152 into the device. The second option is to shield the needle 152 from access. A third option is to break the needle 152 to prevent damage from needle sticks. Other systems, such as active systems, use manual shielding and / or destruction, or manual release of the safety mechanism by an additional button push or similar action. Details of the passive safety embodiment of the present invention are described below.

  One safety embodiment of the present invention is an embodiment of a pull-out design that is passive and fully sealed, such as safety mechanism 108. 5, 10 and 12 are partially cutaway perspective views of the infusion device 100 showing the safety mechanism 108 before activation, after activation, and after deployment of the safety mechanism 108, respectively.

  When the injection device 100 is removed from the skin, the flexible adhesive pad 264 (adhered to both the bottom surface of the bottom enclosure 104 and the bottom surface of the safety mechanism 108) pulls out the safety mechanism 108 before releasing the skin surface. The safety mechanism 108 is locked in place. 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, a safety mechanism 108, for example as shown in FIG. 13, includes a flat surface portion 268 that contacts the patient's skin. The flat surface 268 is where a portion of the adhesive pad 264 (shown in dotted lines in FIG. 13) is affixed to the safety mechanism 108 so that when the patient removes the injection device 100 from the skin, the adhesive pad 264 is removed from the injection device 100. It serves to deploy the safety mechanism 108, thereby shielding the microneedles 152. Otherwise, the microneedle 152 will be exposed after removing the injection device 100 from the patient. When fully extended, the safety mechanism 108 locks in place to prevent accidental injury or exposure to the microneedles 152.

  According to one embodiment, the adhesive pad 264 is provided substantially as two parts, one on the majority of the bottom surface of the bottom enclosure 104 and one on the bottom surface of the safety mechanism 108. When the injection device 100 is removed, the two patches move independently and the safety mechanism 108 is rotatable relative to the bottom enclosure 104. According to another embodiment, the two parts are formed as a single piece of flexible adhesive pad 264, one part is disposed over the majority of the bottom surface of the bottom enclosure 104, and the other part is a safety mechanism. 108 is disposed on the bottom surface.

  According to one embodiment, the safety mechanism 108 is a stamped metal part. According to other embodiments, the safety mechanism 108 is made of substantially the same material as the bottom enclosure 104. As shown in FIG. 14, the safety mechanism 108 is disposed at a front shielding portion 272, a pair of insertion tabs 276 disposed at a rear portion of the safety mechanism 108, and an upper rear end portion of the edge 284 of the safety mechanism 108. A pair of pivot tabs 280, a guide post 288 extending upward from the substantially flat bottom inner surface of the safety mechanism 108, and a locking post 292 also extending upward from the bottom inner surface of the safety mechanism 108 are included. The front shield 272 extends above the edge 284 and shields the patient from the microneedles 152 when the safety mechanism 108 is deployed. The guide post 288 includes a notch inside. The notch engages a protrusion 296 that holds the safety of the rotor 136 when the rotor 136 is in a pre-operation position (eg, as shown in FIGS. 7 and 9), so that the safety mechanism 108 is Will not expand.

  Further, 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 enclosure 104 and provides a space for the microneedles 152 to move. The locking posts 292 are each provided adjacent to the front side edge of the needle opening 156. The bottom enclosure 104 is positioned adjacent to guide post openings 304 (eg, as shown in FIGS. 7 and 9) and opposite side edges of the bottom enclosure 104 (eg, one of which is shown in FIG. 4). Insertion tab openings 308 and a pair of pivot rests 312 disposed on opposite sides of the bottom enclosure 104 (eg, shown in FIGS. 7 and 9).

Referring again to FIG. 14, the insertion tabs 276 include a connection portion 316 and an extension portion 320, respectively. According to one embodiment, the connecting portion 316 extends from the bottom inner surface of the safety mechanism 108 toward the back of the infusion device 100 at an angle that is not perpendicular to the bottom inner surface of the safety mechanism 108. The extension portions 320 extend from the connecting portion 316 substantially vertically toward the outside of each of the safety mechanisms 108. To assemble the safety mechanism 108 to the bottom enclosure 104, hold the safety mechanism 108 at about 45 ° relative to the bottom enclosure 104 and insert the insertion tab 276 through the opening 308 in the insertion tab. The guide post 288 is then inserted through the guide post opening 304 and the safety mechanism 108 is rotated to a predetermined position so that the bottom inner surface of the safety mechanism 108 contacts substantially parallel to the bottom surface of the bottom enclosure 104.

Referring again to FIGS. 7 and 9, these drawings show the rotor 136 in the operating position, but the exploded state of FIGS. 7 and 9 illustrates the process of assembling the safety mechanism 108 to the bottom enclosure 104. Convenient to. However, it will be appreciated that the safety mechanism 108 must be assembled to the bottom enclosure prior to operation. As shown in FIG. 4, after rotating the safety mechanism 108 upward, the safety mechanism 108 is translated backward relative to the bottom enclosure 104 so that the swivel tab 280 causes the respective front edge of the swivel rest 312 to move. Over the pivot rest 312 and a locking post 292 is positioned adjacent to the side edge of the opening 300 in the bottom enclosure 104 and a protrusion 296 that retains the safety of the rotor 136 engages the guide post 288. It becomes like this.

  Referring to FIG. 14, each of the locking posts 292 includes a post extension 324 that extends substantially vertically from the flat bottom inner surface of the safety mechanism 108, and a wedge-shaped portion disposed at the end of the post extension 324. 328. The wedge-shaped portion 328 also increases in width as the height increases relative to the bottom inner surface of the safety mechanism 108.

As the safety mechanism 108 deploys and rotates downward relative to the bottom enclosure 104, the wedge-shaped portion 328 acts against each side edge of the opening 300 in the bottom enclosure 104, thereby causing the locking posts 292 to move toward each other. Elastically deforms toward When safety mechanism 108 is fully deployed, pivot tab 280 is secured within pivot rest 312. Further, the edge of the wedge-shaped portion 328 passes through the bottom edge of the opening 300, and the locking post 292 suddenly returns to a substantially undeformed state, thereby producing a clearly audible sound and feeling a squeak, It is communicated that the safety mechanism 108 is fully positioned and thus the microneedle 152 is covered. Referring back to FIGS. 11 and 12, when the safety mechanism 108 is fully deployed and the locking post 292 suddenly returns to a substantially undeformed state, the upper edge of the wedge-shaped portion 328 is adjacent to the bottom of the opening 300. Engage with the bottom surface of the enclosure 104, thereby preventing the safety mechanism 108 from rotating upward relative to the bottom enclosure 104 and preventing exposure of the microneedles 152. Further, as described above, the front shielding part 272 shields the patient from the microneedle 152.

  Thus, the safety mechanism 108 is an embodiment of a passive safety mechanism that is provided as a single piece and provides a good lock that is not crushed under human load. With this passive safety mechanism, no additional force is applied to the skin during injection, and the microneedle 152 is safely held in the infusion device 100 after use.

  After use of the infusion device 100, the patient can test the device again to ensure that the full dose has been delivered. In this regard, according to one embodiment shown in FIGS. 15A-D, infusion device 100 includes a dose end indicator (EDI) 124. The EDI 124 includes a main body or post 332, a first arm 336 and a second arm 340 that extend substantially horizontally relative to the top of the main body 332.

  The EDI 124 further includes a spring arm 344 that curves upward from the top of the main body 332. According to one embodiment, the spring arm 344 pushes the bottom side of the reservoir subassembly 120, thereby elastically biasing the EDI 124 toward the bottom enclosure 104, for example during shipping and handling of the infusion device 100. It is ensured that the EDI 124 does not move freely out of the infusion device 100. According to one embodiment, the spring arm 344 pushes the bottom side of the dome 176.

  Referring back to FIG. 4, the main body 332 is disposed within the EDI channel 348 and translates substantially vertically within the EDI channel 348. According to one embodiment, the EDI channel is positioned adjacent to one of the recessed channels 204 that guide the leg 208 and the distal end 212 of the plunger 144. The first arm 336 extends across the top of the recessed channel 204.

  Referring back to FIG. 15A, a vertical protrusion or cue post 352 extends upward from the end of the second arm 340. When the contents of the sump are delivered, a cueing post 352 extends through the EDI opening 356 in the upper enclosure 116 (see, eg, FIG. 15C) to signal that the end of the dose has been reached. According to one embodiment, EDI 124 is formed as a unitary structure.

As shown in FIG. 15B, when the plunger 144 is moved upward within the cylindrical housing 200 by the pressure spring 140 after activation, one of the end portions 212 of the plunger 144 contacts the first arm 336 of the EDI 124. The distal end 212 lifts the EDI 124 upward and overcomes the bias of the spring arm 344, so that a post 352 that signals during delivery of the contents of the sump progressively extends through the EDI opening 356. Referring back to FIG. 10, a post 352 that signals is partially extended from the infusion device 100 when drug is pushed out of the reservoir 160 after actuation. When delivery of the contents of the sump is complete and the plunger has reached its full stroke, the vertical protrusion or cueing post 352 is fully extended, as shown in FIG. 15D. Thus, EDI 124 uses the linear motion of plunger 144 to generate a linear motion of EDI 124 that signals delivery of the contents of the sump visible from outside of infusion device 100.

  FIGS. 16A and 16B illustrate another end of dose indicator (EDI) 360 and its operation within the infusion device 100. FIG. As shown in FIG. 16A, the base 364 of the post 368 that signals the EDI 360 is of a different color than the rest of the post 368 that signals. As shown in FIG. 16B, the appearance of the base 364 from outside the infusion device 100 is a signal that drug delivery has been substantially completed. In other respects, EDI 360 is substantially similar to EDI 124.

  17A, 17B show yet another dose end indicator (EDI) 372. FIG. As shown in FIGS. 17A and 17B, the EDI 372 includes a main body 376, a first arm 380 extending from the main body 376, and a first spring arm 384 and a second spring arm also extending from the main body 376. 388. Further, a cue post 392 extends from the end of the first arm 380. According to one embodiment, the cue post 392 includes a base 396 and an upper portion 400. According to one embodiment, at least a portion of the base 396 has a different color than the rest of the post 392 that signals. In such an embodiment, the appearance of different colored portions of the base 396 from outside the infusion device 100 is a signal that drug delivery has been substantially completed.

  As shown in FIG. 17A, EDI 372 further includes a pair of stabilizing arms 412, 416 extending from main body 376. Stabilizing arms 412, 416 stabilize it during operation of EDI 372. FIG. 18 shows an EDI 372 placed in the infusion device. As shown in FIG. 18, the cylindrical housing 200 includes a channel 420 that movably accommodates the main body 376 of the EDI 372. Stabilizing arms 412, 416 contact the outer surface of cylindrical housing 200 and stabilize it during operation of EDI 372.

  As the plunger 144 moves within the cylindrical housing 200 after actuation, the distal end 212 of the plunger 144 contacts and lifts the main body 376 of the EDI 372, thereby causing the movement of the plunger 144 to follow the movement of the main body 376. It is converted into the motion of a post 392 that gives a signal.

  The first spring arm 384 and the second spring arm 388 have spring arm posts 404, 408, respectively, disposed at their respective ends. According to one embodiment, the spring arm posts 404, 408 contact the bottom side of the sump subassembly 120 and, in conjunction with the spring arms 384, 388, resiliently bias the EDI 372 inward relative to the upper enclosure 116. And ensure that the EDI 372 does not extend out of the infusion device 100 before the end of the dose, for example during shipping and handling of the infusion device 100. According to one embodiment, the spring arm posts 404, 408 push the bottom side of the dome 176.

  When the plunger 144 reaches the end of its travel, the force of the pressure spring 140 on the plunger 144 overcomes the bias of the first spring arm 384 and the second spring arm 388, thereby signaling the post 392 is extended out of the infusion device 100, signaling that the delivery of the drug has been substantially completed.

  19A and 19B show yet another dose end indicator (EDI) 424 and its operation, respectively. As shown in FIG. 19A, EDI 424 includes a post 428 having a helical surface 432. EDI 424 includes an arm 436 extending from the end of post 428 and a vertical protrusion or cue post 440 extending from the end of arm 436. The cue post 440 passes through the EDI opening 444 (see FIG. 20A) of the upper enclosure 116 and is thereby visible from outside the infusion device 100. According to one embodiment, EDI opening 444 is an arcuate slot. Post 428 further includes a base 448 for rotatably coupling EDI 424 to bottom enclosure 104.

  FIG. 19B shows a helical surface 432 that contacts the side edge of the plunger 144. FIG. 20A shows the injection device 100 in a pre-operation state. According to one embodiment, the helical surface 432 of the EDI 424 bears the edge of the plunger 144 while the plunger is moving. Thus, as the plunger 144 moves up in the cylindrical housing 200 after actuation, contact between the edge of the plunger 144 and the helical surface 432 causes the EDI 424 to rotate. According to one embodiment, the interaction of the helical surface 432 and the edge of the plunger 144 during movement of the plunger 144 causes less than one full rotation of the post 428. In other words, the pitch of the helical surface 432 causes less than one full rotation of the post 428 during movement of the plunger 144.

  As the EDI 424 rotates, the cue post 440 rotates in the EDI opening 444 correspondingly. When the cueing post 440 reaches the end of the EDI opening 444 as shown in FIG. 20B, the EDI 424 indicates that delivery of the drug is substantially complete.

  Similar to FIGS. 19A and 19B, FIGS. 21A and 21B show yet another dose end indicator (EDI) 452 and its operation. As shown in FIG. 21A, EDI 452 includes a post 456 having a helical surface 460. Further, post 428 has a base 462 for rotatably connecting EDI 452 to bottom enclosure 104. The EDI 452 further includes an indicator 464 that signals the top thereof. A cue indicator 464 passes through the EDI opening 468 (see FIG. 22A) of the upper enclosure 116 and is thereby visible from outside the infusion device 100.

FIG. 21B shows a helical surface 460 that contacts the side edge of the plunger 144. FIG. 22A shows the injection device 100 in a pre-operation state. According to one embodiment, the helical surface 460 of EDI 452 bears the edge of the plunger 144 while the plunger is moving. Thus, when the plunger 144 moves up in the cylindrical housing 200 after actuation, the EDI 452 rotation is caused by contact of the edge of the plunger 144 and the helical surface 460. Compared to EDI 424 of FIG. 19A, spiral surface 460 has a finer pitch. Thus, EDI 452 rotates more than during the stroke of plunger 144 and EDI 424. According to one embodiment, the interaction of the helical surface 460 and the edge of the plunger 144 during movement of the plunger 144 causes at least one full rotation of the post 456. In other words, the pitch of the helical surface 460 causes at least one full rotation of the post 456 during movement of the plunger 144. According to one embodiment, EDI 452 rotates more than one full rotation during the stroke of plunger 144.

  According to one embodiment, the indicator 464 that signals is, for example, an arrow. Correspondingly, there is at least one marker 472 on the outer portion of the upper enclosure 116 adjacent to the EDI opening 468. As the EDI 452 rotates within the EDI opening 468 due to the stroke of the plunger 144, the relative rotation of the indicator 464 that signals the marker 472 is visible from outside the infusion device 100, thereby indicating the progress of drug delivery.

  According to one embodiment, the pitch of the helical surface 460 is determined to cause a slightly less than at least two full rotations of the post 456 during the stroke of the plunger 144. Thus, as shown in FIG. 22B, after moving slightly less than two full revolutions, EDI 452 indicates that drug delivery is substantially complete.

  As shown in FIGS. 23A-23C, various markers can be used to indicate drug delivery progress adjacent to the EDI opening in the upper enclosure 116. For example, FIG. 23A shows a marker 476 that includes a stepped scale. Such a marker 476 paired with an EDI opening can be used with EDI 424. However, it will be appreciated that in general, different markers may be used with different shapes of EDI apertures and different EDI embodiments.

  FIG. 23B shows a marker 480 that includes an icon that displays the full state of the sump 160. For example, one icon indicates that the reservoir 160 is substantially full, and an intermediate icon is that the reservoir 160 is substantially half full, and thus drug delivery is substantially half completed. The third icon indicates that the reservoir 160 is substantially empty and therefore the delivery of the drug is substantially complete.

  FIG. 23C shows a marker 484 that includes a fraction icon indicating the fullness of the reservoir 160, ie, the fraction of completed drug delivery, that changes depending on the direction of rotation of the corresponding EDI. For example, when a clockwise rotating EDI with an indicator that signals by an arrow is used with the marker 484, such EDI movement indicates the reservoir 160 is full. In contrast, when a counterclockwise rotating EDI with an indicator that signals with an arrow is used with marker 484, such EDI movement will indicate the fraction of completed drug delivery.

  Figures 24A and 24B illustrate yet another dose end indicator (EDI) 488 and its operation. According to one embodiment, EDI 488 is a pressure sensitive strip 488. When the plunger 144 reaches the end of its travel, the pressure of the plunger 144 (due to the force of the pressure spring 140) is brought to the pressure sensitive strip 488. The pressure on the pressure sensitive strip 488 causes a color change, thereby indicating that drug delivery is substantially complete. Since the top of the reservoir (eg the window there) is transparent, the color change can be seen.

  According to one embodiment, EDI 488 is disposed on the inner surface of, for example, a transparent dome 176 within reservoir 160. At the end of the travel of the plunger 144, the pressure of the plunger 144 against the reservoir dome seal 164 is transmitted by the reservoir dome seal 164 to the pressure sensitive strip 488, thereby causing a color change.

  24A and 25A show the injection device 100 in a state before operation. According to one embodiment shown in FIGS. 24A and 25A, the EDI 488 is positioned within the body of the infusion device 100 so that it can be viewed from outside the infusion device 100. Further, the EDI 488 is configured such that when the plunger 144 reaches the end of its travel, the distal end 212 of the plunger 144 contacts the pressure sensitive strip 488 by the force of the pressure spring 140, and the pressure of the distal end 212 against the pressure sensitive strip 488. Are arranged to cause a color change of the pressure sensitive strip 488. FIGS. 24B and 25B show the infusion device 100 after the end 212 has contacted the pressure sensitive strip 488 and caused a color change, indicating the completion of drug delivery.

  FIGS. 26A and 26B show another end of dose indicator (EDI) 492 and its operation. According to one embodiment, EDI 492 is a dye pack having at least two separate chambers 496,500. When the plunger 144 reaches the end of its travel, the pressure of the plunger 144 (due to the force of the pressure spring 140) is exerted on the dye pack 492, thereby rupturing the partition 504 between the two chambers 496, 500. . When the partition 504 ruptures, the contents of the two chambers 496, 500 mix and the color of the mixture changes, thereby indicating that drug delivery is substantially complete.

  According to one embodiment, chamber 496 has a yellow dye and chamber 500 has a blue dye. When the partition 504 ruptures, the blue and yellow dyes mix to form a green dye, thereby indicating that drug delivery is substantially complete.

  According to one embodiment, EDI 492 is disposed on the inner surface of, for example, a transparent dome 176 in reservoir 160. At the end of the travel of the plunger 144, the plunger pressure against the reservoir dome seal 164 is transmitted to the dye pack 492 by the reservoir dome seal 164, thereby causing its color change.

  26A and 27A show the injection device 100 in a state before operation. According to one embodiment shown in FIGS. 26A and 27A, the EDI 492 is disposed within the body of the infusion device 100 so that it can be seen from outside the infusion device 100. Further, when the plunger 144 reaches the end of its travel, the EDI 492 is brought into contact with the dye pack 492 by the force of the pressure spring 140 and the partition 504 is moved by the pressure of the end 212 against the dye pack 492. Rupture causes a color change in the dye pack. FIGS. 26B and 27B show the infusion device 100 after the end 212 has contacted the dye pack 492 and caused a color change, indicating the completion of drug delivery.

  FIG. 28 illustrates one embodiment of an infusion device 700 with an injection port 704. The injection port provides access to an empty or partially filled reservoir 708 that allows the patient to place a substance or combination of substances into the reservoir prior to activation. Alternatively, a pharmacist or pharmacist can use injection port 704 to fill infusion device 700 with a substance or combination of substances prior to sale. In virtually every other respect, the injection device 700 is similar to the injection device 100 already described.

  Next, the operation of the injection device 100 will be described. The above-described embodiments of the present invention preferably include a push button (actuation button 128) design. The infusion device 100 can be positioned and affixed to the skin surface and activated and / or activated by pressing the activation button 128. More specifically, in the first step, the patient removes the device from the sterile package (not shown) and removes the cover (not shown) of the adhesive pad 264. The patient further removes the needle cover 112. After removing the infusion device 100 from the package and prior to use (see, eg, FIGS. 1, 2, 4, and 5), the infusion device 100 in a pre-actuated state allows the patient not only to see the device but also its contents The components can be examined for missing or damaged components, including one or more expiration dates, drug haze or color change.

  The next step is to position and affix the infusion device 100 to the patient's skin surface. Like a medicinal patch, the patient presses the infusion device 100 firmly against the skin. One side of the adhesive pad 264 adheres to the bottom surface of the bottom enclosure 104 and the bottom surface of the safety mechanism 108, and the opposite side of the adhesive pad 264 secures the infusion device 100 to the patient's skin. These bottom surfaces (of the bottom enclosure 104 and safety mechanism 108) can be flat, conform to the shape of the body, or any suitable shape on which the adhesive pad 264 is secured. According to one embodiment, prior to shipping, a cover of adhesive pad 264, such as a film, is applied to the patient side of adhesive pad 264 so as to maintain adhesiveness during shipping. As described above, prior to use, the patient removes the adhesive cover to expose the adhesive pad 264 for placement on the skin.

After removing the adhesive cover, the patient can place the infusion device 100 on the skin and press to ensure proper adhesion. As described above, the device is activated by pressing the activation button 128 after being properly positioned. This actuating step releases the plunger 144 and the pressure spring 140, thereby allowing the plunger 144 to push the flexible film (reservoir dome seal 164) of the reservoir 160 and pressurizing the reservoir. The This actuating step also serves to release the drive spring 148 from the drive spring holder 260 of the rotor 136 so that the microneedle 152 is removed from the infusion device 100 (opening 300 in the bottom enclosure 104 and needle opening in the safety mechanism 108). The microneedle 152 is placed on the patient extending (through 156). In addition, the actuation step opens valve 168 to establish a fluid communication path (eg, see FIGS. 8-10) via channel arm 172 between reservoir 160 and microneedles 152. A big advantage is that each operation can be realized by one push button operation. Yet another significant benefit is the use of a continuous fluid communication path that is entirely contained within the sump subassembly 120.

When activated, the patient typically leaves the infusion device 100 in place for a period of time (eg, 10 minutes to 72 hours), ie, wears the device so that the contents of the reservoir are completely delivered. The completion of drug delivery is then indicated by EDI, for example EDI 124. The patient then removes and discards the device without damaging the underlying skin or tissue. If intentionally or accidentally removed, one or more safety features are deployed to shield the exposed microneedles 152. More specifically, when the patient removes the infusion device 100 from the skin, the adhesive pad 264 acts to deploy the safety mechanism 108 from the infusion device 100, thereby shielding the microneedle 152, otherwise the microneedle 152. Will be exposed after removal of the infusion device 100 from the patient. When fully extended, the safety mechanism 108 locks in place, thereby preventing accidental injury or exposure to the microneedles 152. However, the safety function can be configured not to deploy when the activation button 128 is not pressed and the microneedle 152 is not extended, thereby preventing the safety mechanism from being deployed before use. After use, the patient can test the device again to ensure that the full dose has been delivered. For example, the patient can look inside the reservoir through a transparent dome 176 and / or examine the EDI 124.

  The above-described embodiments are suitable for use in administering various substances, including drugs and drugs, to patients, particularly human patients. As used herein, a drug includes a biologically active substance that can be delivered through body membranes and surfaces, particularly the skin. Examples listed in more detail below include antibiotics, antiviral agents, analgesics, anesthetics, appetite suppressants, anti-arthritic agents, antidepressants, antihistamines, anti-inflammatory agents, anti-neoplastic agents, DNA vaccines. There are vaccines to include. Other substances that can be delivered intradermally or subcutaneously to the patient include human growth hormone, insulin, proteins, peptides and fragments thereof. Proteins and peptides can be naturally occurring, synthetic products, or recombinant products. Furthermore, this device can be used during intradermal injection of dendritic cells in cell therapy. Other substances that can be delivered according to the method of the invention can be selected from the group consisting of drugs, vaccines, etc. used in the prevention, diagnosis, reduction, treatment, therapy of disease. Drugs used with these include α1-antitrypsin, anti-angiogenic agents, antisense, butorphanol, calcitonin and analogs, Seredes, COX-II inhibitors, dermatologic agents, dihydroergotamine, dopamine agonists and dopamine antagonists, enkephalins And other opioid peptides, epidermal growth factor, erythropoietin and the like, follicle stimulating hormone, G-CSF, glucagon, GM-CSF, granisetron, growth hormone and analogues (including growth hormone releasing hormone), growth hormone antagonists, Hirudin analogues such as hirudin and hirulog, IgE inhibitors, insulin, insulinotropin and analogues, insulin-like growth factor, interferon, interleukin, luteinizing hormone, luteinizing hormone Releasing hormones and analogues, low molecular weight heparin, M-CSF, metoclopramide, midazolam, monoclonal antibodies, narcotic analgesics, nicotine, non-steroidal anti-inflammatory agents, oligosaccharides, ondansetron, parathyroid hormone and the like , Parathyroid hormone antagonist, prostaglandin antagonist, prostaglandin, recombinant soluble receptor, scopolamine, serotonin agonist and serotonin antagonist, sildenafil, terbutaline, thrombolytic agent, tissue plasminogen activator, Carrier / adjuvant vaccines, including TNF and TNF antagonists, prophylactic and therapeutic antigens, or carrier / adjuvant free vaccines (subunit proteins, peptides and polysaccharides, polysaccharide conjugates, toxoids, genetic vaccines, attenuated toxicity, Re Aggregate, inactivated, whole cell, viral and bacterial vectors). These include addiction, arthritis, cholera, cocaine addiction, diphtheria, tetanus, HIB, Lyme disease, meningitis, measles, mumps, rubella, chickenpox, yellow fever, respiratory multinuclear virus, tick-mediated Japanese encephalitis, Hepatitis including pneumococci, streptococci, typhoid, influenza, A, B, C, and E, otitis media, rabies, polio, HIV, parainfluenza, rotavirus, Epstein-Barr virus, CMV, chlamydia, by type Related to incompetent hemophilus, Moraxella catarrhalis, human papillomavirus, tuberculosis including BCG, gonorrhea, asthma, atherosclerotic malaria, E. coli, Alzheimer, Helicobacter pylori, salmonellosis, diabetes, cancer, herpes simplex, human papilloma . Other substances include all major therapeutic agents, such as agents for colds, anti-addiction agents, anti-allergic agents, antiemetics, anti-obesity agents, anti-osteoporosis agents, anti-infective agents, analgesics, anesthetics , Appetite suppressant, anti-arthritis drug, anti-asthma drug, anti-epileptic drug, antidepressant drug, anti-diabetic drug, anti-histamine drug, anti-inflammatory drug, anti-migraine drug, motion sickness drug, anti-emetic drug, anti-neoplastic drug Antiparkinsonian, antipruritic, psychotic, antipyretic, anticholinergic, benzodiazepine antagonist, systemic blood vessels, coronary arteries, peripheral blood vessels, vasodilators including cerebral blood vessels, bone agonists, central nervous system stimulants, hormones, hypnosis Drugs, immunosuppressants, muscle relaxants, parasympatholytics, parasympathomimetics, prostaglandins, proteins, peptides, polypeptides and other macromolecules, stimulants, sedatives, hyposexual and tranquilizers, and tuberc Down there is a major diagnostic agents and other hypersensitivity drugs. These are those described in the literature (see, for example, Patent Document 1 entitled “Method of Intradermally Injecting Substances”, the entire contents of which are expressly incorporated herein by reference).

  Vaccine formulations that can be delivered according to the systems and methods of the invention can be selected from the group consisting of antigens or antigen compositions that can elicit an immune response against human pathogens. These antigens or antigen compositions include human herpesvirus (HSV), cytomegalo, such as HIV-1 (such as tat, nef, gp120 or gp160), gD or its derivatives or immediate early proteins such as ICP27 from HSV1 or HSV2. Virus (especially human) CMV (such as gB or a derivative thereof), rotavirus (including live attenuated virus), Epstein-Barr virus (such as gp350 or a derivative thereof), varicella-zoster virus (VZV: gpl, II, and IE63) Or from hepatitis viruses such as hepatitis B virus (eg, hepatitis B surface antigen or derivatives thereof), hepatitis A virus (HAV), hepatitis C virus, and hepatitis E virus, or Paramyxovirus, ie breathing Polynuclear viruses (such as RSV: F protein and G protein or derivatives thereof), parainfluenza virus, measles virus, mumps virus, human papilloma virus (HPV: eg HPV 6, 11, 16, 18), flavivirus (eg yellow Fever virus, dengue virus, tick-borne encephalitis virus, Japanese encephalitis virus), or influenza virus (live virus or whole inactivated virus, isolated influenza virus grown in eggs or MDCK cells, or whole influenza virosome, or its From other viral pathogens such as purified or recombinant proteins such as HA, NP, NA or M proteins or combinations thereof, Neisseria gonorrhoeae and Neisseri Meningitidis (eg, capsular polysaccharides and conjugates thereof, transferrin-binding protein, lactoferrin-binding protein, PilC, adhesion factor), Neisseria, Streptococcus spiogenes (eg, M protein or fragment thereof, C5A protease, lipotheco Acid), Streptococcus agalactier, Streptococcus mutans, Hemophilus duclay, Moraxella catarrhalis also known as Blanchamella catarrhalis (eg, high and low molecular weight adhesion and invasion factors), Moraxella spp., Bordetella Pertussis (eg, pertactin, pertussis toxin or derivatives thereof, filamentous hemagglutinin, adenylate cyclase, fallopian tube fistula), Bordetella parapartasis, and Bordetebra bron Bordetella genus including chiseptica, Mycobacterium tubaculosis (for example, ESAT6, antigen 85A, antigen 85B, or antigen 85C), mycobacterium bovis, mycobacterium lepre, mycobacterium abium, mycobacterium tuberculosis Rhosis, Mycobacterium genus including Mycobacterium smegmatis, Legionella genus including Legionella pneumophila, Toxigenic Escherichia coli (eg colonization factor, heat-resistant toxin or derivative thereof, heat-resistant toxin or derivative thereof), intestinal bleeding Escherichia, including enteropathogenic E. coli, enteropathogenic E. coli (eg, Shiga toxin-like toxin or derivative thereof), Vibrio genus including Vibrio cholera (eg, cholera toxin or derivative thereof), Shigerazone, Shigella dyscenteri, Shigera lexne Including Shigella, Yersinia enterocolitica (eg, Yop protein), Yersinia pestis, Yersinia, including Yersinia pseudotuberculosis, Campylobacter jejuni (eg, toxins, adhesion factors, and invasion factors) and Campylobacter coli Helicobacter including Campylobacter, Salmonella typhi, Salmonella paratyphi, Salmonella cholera Switzerland, Salmonella genus including Salmonella enteritides, Listeria genus including Listeria monocytogenes, Helicobacter pylori (eg, urease, catalase, vacuolating toxin) Genus, including Pseudomonas arginosa, Pseudomonas genus, Staphylococcus aureus, Staphylococcus epidermides, Enterococcus Sphacharis, Enterococcus genus including Enterococcus faecium, Clostridium tetani (eg, tetanus toxin and derivatives thereof), Clostridium botulinum (eg, botulinum toxin and derivatives thereof), Clostridium difficile (eg, Clostridium toxin A or B and derivatives thereof) Including Clostridium, Bacillus anthracis (eg, Botulinum toxin and its derivatives), Corynebacterium diphseri (eg, Diphtheria toxin and its derivatives), Corynebacterium, Borrelia burgdorferi (eg, OspA, OspC, DbpA, DbpB), Borrelia galini (eg, OspA, OspC, DbpA, DbpB), Borrelia afuseri (eg, Osp A, OspC, DbpA, DbpB), Borrelia under Sony (eg, OspA, OspC, DbpA, DbpB), Borrelia, including Borrelia harmsey, Erecia equi, and Erichia, including human granulocyte Erecia pathogens, Rickettsia rickets Including Rickettsia, Chlamydia trachomatis (eg, MOMP, heparin-binding protein), Chlamydia pneumoniae (eg, MOMP, heparin-binding protein), Chlamydia, including Chlamydia sutasi, Leptospira, including Leptospira tallogans, , Dilute outer membrane proteins), Treponema dentola, Treponema genus including Treponema hyodysenteri, or derived from Plasmodium fal Plasmodium genus including plum, Toxoplasma genus including Toxoplasma gondii (eg, SAG2, SAG3, Tg34), Entoameba genus including Entameba history tec, Babesia genus including Babesia microtti, Trypanosoma genus including Trypanosoma cruzi, Giardiaran Derived from parasites such as Giardia, including Bria, Leishmania, including forested tropical Leishmania, Pneumocystis, including Pneumocystis carini, Trichomonas, including Trichomonas vaginaris, and Cystoma, including Schistosoma mansoni Those derived from yeasts such as Candida genus including Candida albicans and Cryptococcus genus including Cryptococcus neoformans. These are described in the literature (see, for example, Patent Document 2 entitled “Vaccine Delivery System”, the entire contents of which are expressly incorporated herein by reference).

  These also include other preferred specific antigens for Mycobacterium tubaculosis such as Tb Ra12, Tb H9, Tb Ra35, Tb38-1, Erd 14, DPV, MTI, MSL, mTTC2, and hTCC1. . Proteins for Mycobacterium tubaculosis also include fusion proteins and variants thereof. These are the fusion of at least two, preferably three, polypeptides of Mycobacterium tubaculosis into larger proteins. Preferred fusions include Ra12-TbH9-Ra35, Erd14-DPV-MTI, DPV-MTI-MSL, Erd14-DPV-MTI-MSL-mTCC2, Erd14-DPV-MTI-MSL, DPV-MTI-MSL-mTCC2, There is TbH9-DPV-MTI. The most preferred antigens for Chlamydia include, for example, high molecular weight protein (HWMP), ORF3, and putative membrane protein (Pmps). Preferred bacterial vaccines include Streptococcus pneumoniae (eg, capsular polysaccharide and conjugates thereof, PsaA, PspA, streptolidine, choline binding protein) and protein antigen pneumolysin (see, eg, Non-Patent Document 1 and Non-Patent Document 2) and It contains an antigen from the genus Streptococcus containing its mutant detoxification derivative. Other preferred bacterial vaccines include Haemophilus influenza B (“Hib”, eg, PRP and its conjugates), untyped hemophilus influenza, eg, OMP26, high molecular weight adhesion factor, P5, P6, protein D and lipoprotein D, And antigens from the genus Haemophilus, including fimbrins and peptide-derived fimbrins or multiple replicating variants or fusion proteins thereof. Derivatives of hepatitis B surface antigen are well known in the art and include, among other things, the S antigen of PreS1, PreS2. In a preferred embodiment, the vaccine formulation of the invention comprises the HIV-1 antigen, gp120, particularly when expressed in CHO cells. In another embodiment, the vaccine formulation of the invention comprises gD2t as defined above.

  In addition to the delivery of the substances listed above, the infusion device 100 can also be used to withdraw substances from the patient or monitor the level of substance in the patient's body. Examples of substances that can be monitored or withdrawn are blood, interstitial fluid or plasma. The extracted material can then be analyzed for analytes, glucose, drugs, and the like.

  Although only some of the exemplary embodiments of the present invention have been described in detail, many modifications may be made in these exemplary embodiments without departing significantly from the novel teachings and advantages of the present invention. Those skilled in the art will readily understand that this is possible. Accordingly, all such modifications are intended to be included within the scope of the appended claims and their equivalents.

Claims (4)

A drug delivery device comprising:
A main body having a liquid reservoir capable of containing a drug disposed in the main body,
An injection needle that pierces the patient's skin, the injection needle in fluid communication with the reservoir;
A pressure unit;
A plunger capable of moving within the body under the force of the pressurizing unit to discharge the drug from the reservoir;
An indicator means visible from outside the drug delivery device for indicating that the delivery of the medicament is substantially complete,
Movement of the plunger a predetermined distance causes the indicator means to activate a change in color of the indicator means that is visible from outside the drug delivery device;
The plunger moves at least a portion of the predetermined distance without activating the indicator means ;
The indicator means comprises a pressure sensitive strip, and when the plunger reaches the end of its travel, the plunger contacts the reservoir and one of the pressure sensitive strips by the force of the pressure unit. And the pressure of the plunger against the one of the reservoir and the pressure sensitive strip causes a color change of the pressure sensitive strip, indicating that the delivery of the drug is substantially complete. are drug delivery device according to claim Rukoto. The pressure sensitive strip is disposed within the reservoir;
Wherein at the end of the plunger movement stroke, the drug delivery device of claim 1, wherein the color change of the strip of the pressure-sensitive is caused by the pressure of the plunger with respect to said reservoir liquid. The reservoir comprises a transparent dome and a flexible and non-extensible reservoir dome seal;
The pressure sensitive strip is disposed on an inner surface of the dome;
The end of the travel of the plunger, the reservoir dome seal transmits the plunger pressure to the pressure sensitive strip, thereby causing a color change of the pressure sensitive strip. 2. The drug delivery device according to 1. The drug delivery device according to claim 1, wherein the pressure unit includes a pressure spring.