CN104307071B - Self-injection device - Google Patents

Abstract

The invention discloses a self-injection device (100), wherein the device is used for conveying medicament into the body of a patient by injecting into the skin of the patient or injecting and penetrating through the skin of the patient. The device comprises a body (104,116), an injection needle (152), and a pressurization system, wherein the body is provided with a container (160) for accommodating medicament; the container is arranged in the body; the injection needle is used for penetrating into the skin of the patient; the needle (152) is provided with a cavity and is communicated with the container (160); the pressurization system is used for pressurizing the container (160). The device further comprises indicator equipment (124), wherein the indicator equipment can be seen from the outer side of the device (100), and the indicator equipment is used for indicating that medicament conveyance is basically completed.

Description

Injection device

This divisional application is based on Chinese invention patent application number 200980163436.X (international application no PCT/ US2009/006570), denomination of invention " injection device ", the divisional application of the patent application on 16 days December 2009 applying date.

Technical field

The present disclosure relates generally to a kind of material delivery apparatus, which has improved patient convenience, ease for use and effect Rate.The present invention further relates to a kind of paster shape on the whole, is transfused or injection device from holding type material, and described device can be used in Many kinds of substance or medicine are conveyed to patient.More particularly it relates to a kind of paster shape with dosage end indicator is defeated Note or injection device.

Background technology

A large amount of people (people for for example undergoing such as diabetes etc situation) use certain of such as daily infusion of insulin etc The infusion of therapeutic of the form of kind, to maintain the tight control to its blood sugar level.At present, in infusion of insulin treatment example, deposit In the Main Patterns of two kinds of daily insulin therapies.First mode includes syringe and novopen.These devices are using simple And cost is relatively low, but they need pin to prick in per injection, generally three times a day to four times.Second mode includes infusion pump Treatment, this needs the expensive pump that purchase continues about three years.High cost (the 8 of the daily rate that about syringe is treated of pump Times to 10 times) and finite lifetime be that the high of this treatment is hindered.Insulin pump also represents older technology and uses loaded down with trivial details.This Outward, from from the perspective of life style, pump is connected to the pipe fitting in the delivery site of patient's abdominal part, and (referred to as " infusion covers Group ") be it is very inconvenient, and pump it is heavier so that carry pump become burden.But, from from the perspective of patient, use The overwhelming majority in the patient of pump preferably retains pump in its remaining years.This is because infusion pump is although more more complicated than syringe and pen There is provided the advantage that continuous infusion, exact dose and the programmable movement schedule of insulin are arranged.This causes closer blood Sugar control and improved health perception.

The number of times increase of growth and daily injection in view of the treatment of observed pump, for better healing interest just Increasing.In the infusion example and similar infusion example, fully meeting the increase interest, to be desirable for following insulins defeated Send or infusion format：Its best features by the best features (low cost and ease for use) of daily injection treatment with insulin pump (continuous infusion and exact dose) combines, and it also avoid respective shortcoming.

Some trials have been carried out to provide inexpensive and easy to use free-standing or " Wearable " infusion of drug Device.Some in these devices mean partially or completely droppable.In theory, such device can provide infusion The lot of advantages of pump is without thing followed cost and inconvenience.But, unfortunately, being much subjected in these devices is following scarce Point：Discomfort including patient (due to the divider of injection needle that used and/or length), conveyed material with infusion device The compatibility between material used in construction and interact, and correctly do not activated (for example, due to device by patient Premature activation and caused " wet type " injection) in the case of possible failure.Also run in the mill and in control pin Penetration depth in difficulty, especially when the injection needle using short and/or fine divider.To connecting with the device for being used The probability of the needlestick injury of tactile personnel is also always a problem.

The demand of the substitute to current infusion device (such as the infusion pump of insulin) is accordingly, there exist, which enters one Step provides the simplicity of manufacture and improves for insulin and using for non-insulin application.

The content of the invention

It is an aspect of the invention to provide a kind of patch-like infusion or injection device, described device advantageously can be supported Dress by skin, while the infusion for expecting material and the discomfort for providing minimum are provided by using one or more micropins.This The another aspect of invention is to provide this infusion with dosage end indicator or injection device.

The present invention it is above-mentioned and/or other in terms of by provide following apparatus and realize：Described device is used for by injection To in patient skin or it is injected through patient skin and conducts drugs in patient's body, described device includes：Body, described Body has reservoir, and the reservoir is arranged on described in vivo for accommodating medicine；Injection needle, the injection needle are used to pierce Enter the skin of patient, the needle set is had inner chamber and connected with the reservoir；And compression system, the compression system is used for Pressurize the reservoir.Described device also includes can be visible for indicating what drug delivery was substantially finished from the outside of device Pointer device.

The present invention it is above-mentioned and/or other in terms of by provide following apparatus and realize：Described device is used for by injection To in patient skin or it is injected through patient skin and conducts drugs in patient's body, described device includes：Body；Storage Device, the reservoir are arranged on described in vivo for accommodating medicine；Injection needle, the injection needle are used for the skin for being pierced into patient Skin and implement from reservoir medicine；And compression system, the compression system is for the reservoir that pressurizes.The dress Put that also include can be visible for indicating dosage end indicator that drug delivery is substantially finished from the outside of device.

The present invention other and/or other in terms of and advantage partly will explain in the following description, and will be from froming the perspective of Bright middle part apparent, or be appreciated that by the practice of the present invention.

Description of the drawings

From detailed description with reference to the accompanying drawings, embodiments of the invention above-mentioned and/or other in terms of and advantage will more It is easy to understand, wherein：

Fig. 1 illustrates the embodiment of patch-like infusion or injection device under the pre-activated state before activation Axonometric chart；

Fig. 2 illustrates partial exploded view of the infusion device of Fig. 1 under pre-activated state；

Fig. 3 illustrates partial exploded view of the infusion device of Fig. 1 under pre-activated state, and wherein activator appliance button is outwarded winding To show more details；

Fig. 4 illustrates more completely exploded view of the infusion device of Fig. 1 under pre-activated state；

Fig. 5 illustrates sectional view of the infusion device of Fig. 1 under pre-activated state；

Fig. 6 illustrates sectional view of the infusion device of Fig. 1 under pre-activated state, and wherein activator appliance button is outwarded winding；

Fig. 7 illustrates partial exploded view of the infusion device of Fig. 1 during the installation of release mechanism；

Fig. 8 illustrates the infusion device of Fig. 1 partial exploded view after the activation；

Fig. 9 illustrates the infusion device of Fig. 1 more completely exploded view after the activation；

Figure 10 illustrates the infusion device of Fig. 1 sectional view after the activation；

Figure 11 illustrates partial exploded view of the infusion device of Fig. 1 after the expansion of release mechanism；

Figure 12 illustrates sectional view of the infusion device of Fig. 1 after the expansion of release mechanism；

Figure 13 illustrates the basal surface of release mechanism；

Figure 14 further illustrates the structure of release mechanism；

Figure 15 A- Figure 15 D illustrate dosage end indicator and its operation in the infusion device of Fig. 1；

Figure 16 A and 16B illustrate another dosage end indicator and its operation in the infusion device of Fig. 1；

Figure 17 A and 17B illustrate another dosage end indicator；

Figure 18 illustrates the dosage end indicator of Figure 17 A being arranged in the infusion device of Fig. 1；

Figure 19 A and 19B illustrate another dosage end indicator and its operation；

Figure 20 A and 20B illustrate the operation of the dosage end indicator of Figure 19 A in the infusion device of Fig. 1；

Figure 21 A and 21B illustrate another dosage end indicator and its operation；

Figure 22 A and 22B illustrate the operation of the dosage end indicator of Figure 21 A in the infusion device of Fig. 1；

Figure 23 A-23C are illustrated for indicating the embodiment of the labelling of drug delivery process；

Figure 24 A and 24B illustrate another dosage end indicator and its operation；

Figure 25 A and 25B illustrate the operation of the dosage end indicator of Figure 24 A in the infusion device of Fig. 1；

Figure 26 A and 26B illustrate another dosage end indicator and its operation；

Figure 27 A and 27B illustrate the operation of the dosage end indicator of Figure 26 A in the infusion device of Fig. 1；

Figure 28 illustrates the embodiment of the infusion device with injection port.

Specific embodiment

Reference will now be made in detail to now embodiments of the invention, the example illustration of the present invention in the accompanying drawings, wherein, identical accompanying drawing Labelling represents identical element all the time.The embodiment makes the present invention instantiating by referring to accompanying drawing.

The embodiment of present invention described below can act as easily, patch-like infusion or injection device 100 with The material of predicted dose, such as liquid medicine or medicament are conveyed in a period of time or disposably to patient fully.The device is excellent Selection of land is supplied to end user with pre-filled state (i.e. medicine or medicament are had been positioned in the reservoir of device).Although herein Described patch-like infusion or injection device 100 (for example, shown in Fig. 1) can be adopted by patient and/or caretaker, but For convenience, the user of the device is hereinafter referred to as " patient ".In addition, for convenience, such as " vertical " and " level " and " top The term in portion " and " bottom " etc is used to represent the relative direction with regard to arranging infusion device 100 on a horizontal surface.But It is, it should be appreciated that infusion device 100 is not limited to this direction, and infusion device 100 can be used for any direction.Separately Outward, the replacement of term " infusion device " and " injection device " is not intended as limiting using the device for describing the enforcement present invention Property.Not with falling within the scope of the present invention from the infusion device of injectability, the injection device of continuous infusion is not performed Fall within the scope of the present invention.For convenience, but without limitation, in the following description using term " infusion device ".

The patch-like infusion device 100 of Fig. 1 is from holding type and viscous on the basal surface of infusion device 100 by being arranged on Conjunction portion is attached to the skin surface (as will be described in more detail below) of patient.Once being properly positioned and being activated by patient, release Pressure of the loose spring effect in the flexible reservoir in device can be used in passing through one or more patient's pins via pin manifold (for example, micropin) empties the content of reservoir.Material in reservoir is subsequently defeated by the micropin being driven in skin Send through patient skin.It should be appreciated that other embodiment is possible, wherein spring is replaced by different types of energy storage dress Put, these energy storage devices can substantially be machinery, electronics and/or chemistry.

As will be determined by the skilled person understood, there is construction and use patch-like infusion device disclosed herein 100 number of ways.Although the embodiment and description below of middle description with reference to the accompanying drawings, embodiment disclosed herein is simultaneously The non-various optional design and embodiment for meaning that limit includes by the disclosed invention.In each open embodiment, the device quilt Referred to as infusion device, but the device also can be with the speed fast a lot (big preparations) than generally being realized by typical infusion device Speed injection mass.For example, content can be as short as several seconds or grow being conveyed to the period of several days.

In the embodiment of the device shown in Fig. 1 to Figure 12, the push-button design of patch-like infusion device 100 is shown, Wherein, the activation of device and excitation is realized with single multi-functional/step process.Fig. 1 illustrates defeated under pre-activated state The assembled embodiment of dispensing device 100.Fig. 2-Fig. 6 illustrates the partial exploded view of the infusion device 100 under pre-activated state And sectional view, Fig. 7 illustrates partial exploded view of the infusion device 100 during the installation of release mechanism, and Fig. 8-Figure 10 is illustrated The exploded view after the activation of infusion device 100 and sectional view, and Figure 11 and Figure 12 illustrate infusion device 100 in release mechanism Exploded view and sectional view after expansion.Infusion device 100 is configured in pre-activated state (for example, institute in Fig. 1, Fig. 2 and Fig. 5 Show), activation or excited state (for example, shown in Fig. 8-Figure 10) and retract or safe condition (for example, institute in Figure 11 and Figure 12 Show) between operate.

As shown in fig. 1, the embodiment of patch-like infusion device 100 includes bottom enclosure 104, release mechanism 108, flexibility Needle cover 112, top casing 116, reservoir sub-component 120, dosage end indicator (EDI) 124, and activator appliance button 128, swash Device button living 128 includes patient interface surface 132.In addition, as shown in Fig. 2-Fig. 6, infusion device 100 also includes rotor or swashs Ring 136 living, pressing spring 140, arch metal plunger 144, and driving spring 148.

Flexible needle cover 112 is by protecting at least one pin 152 (being described in more detail below) and providing aseptic barrier portion And the safety of patient and device is provided.Needle cover 112 protects pin 152 during device manufacture, protects patient before the use, and Any time before the removal provides aseptic barrier portion.According to one embodiment, needle cover 112 attaches to pin discrimination via press-fit Pipe, at least one pin 152 are arranged in the pin manifold.In addition, according to one embodiment, the pin opening 156 of release mechanism 108 (being described in more below) is shaped to closely corresponding with the periphery of needle cover 112.

For example, as shown in Fig. 2, Fig. 3, Fig. 5, Fig. 6, Fig. 8, Figure 10 and Figure 12, reservoir sub-component 120 includes reservoir 160th, reservoir arched sealing member 164, valve 168, at least one pin 152, and be arranged between valve 168 and pin 152 and at them Between produce flow path at least one passage 172 (for example, with reference to Fig. 8).Reservoir 160 includes vault 176.In addition, storage Storage sub-component 120 includes removable needle cover 112 optionally to cover at least one pin 152.According to one embodiment, storage Storage sub-component 120 also includes reservoir arm sealing member 180, so as to cover passage 172.Preferably, pin 152 include pin manifold and Many micropins 152.

For example, as shown in Figure 5, the reservoir arched sealing member (flexible membrane) 164 of reservoir sub-component 120 is arranged on post Between plug 144 and vault 176.Reservoir contents (for example, medical material) for infusion device 100 are arranged on and encircle between reservoir In space between shape sealing member 164 and vault 176.Reservoir arched sealing member 164, vault 176 and the space between them Combination limit reservoir 160.Vault 176 is preferably transparent can observe reservoir contents.Reservoir arch is close Sealing 164 can be made up of on-expansible material or laminated material (such as metal coating or other similar substances).For example, Neng Gou A kind of possible flexible layer press mold used in reservoir arched sealing member 164 includes the first polyethylene layer, as in this area Second chemosphere known to technical staff with provide attachment means for the 3rd metal level to being chosen based on barrier feature, And including the 4th layer of polyester fiber and/or nylon.By (for example, 176) vault is utilized in conjunction with metal with rigid element Plated film or metalized film, improve the barrier properties of reservoir 160, so as to increase or improve the guarantor of the content being accommodated within The matter phase.For example, when reservoir contents include insulin, the dominant touch material in reservoir 160 includes linea low density Polyethylene (LLDPE), Low Density Polyethylene (LDPE), cyclic olefine copolymer (COC) and Teflon.Following article is described in more detail , the dominant touch material in the remaining flow path of reservoir contents may also include COC and LLDPE and thermoplastic Property elastomer (TPE), medical grade acrylic acid, rustless steel and pin binding agent (for example, the binding agent of UV solidifications).With reservoir 160 Content keep extending this material of contact preferably by ISO10-993 and other applicable biocompatibility tests.

Reservoir sub-component 120 preferably in enforceable controlled environment reservoir contents the regulation shelf-life It is interior to store without deleteriously affecting content, and can apply in a variety of environmental conditions.In addition, by reservoir The barrier portion that the part of component 120 is provided is impermissible for gas, liquid and/or solid material with than meeting desired shelf-life institute During the big speed of the speed allowed is transported to content or it is carried out content.In embodiments shown above, equipment is stored Material can be stored within the temperature range of about 34 degrees Fahrenheits to 120 degrees Fahrenheits and be operated, and can have 2 years or 2 years Shelf-life above.

In addition to meeting stability requirement, reservoir sub-component 120 can also be successfully passing any number of leakage Test (sample of 30psi is kept into 20 minutes No leakages for example) and guarantee operation.As described in more detail below, stem from Other fillings of the configuration of reservoir, storage and convey benefit and include the head space of adaptability and reduction.

In one embodiment, reservoir 160 is emptied before filling.By emptying reservoir 160 simultaneously before filling And only there is in vault 176 slight recess, the excessive waste and head space in reservoir 160 can be preferably minimized. In addition, the shape of reservoir can be configured to type (for example, pressing spring 140 and the plunger of the excitation mechanism for being suitable to used 144).In addition, using the flexible reservoir 160 being drained reducing in the reservoir 160 filled during filling Any air or bubble.(this can undergo the change of external pressure or temperature in infusion device 100 using flexible reservoir 160 Cause increase reservoir internal pressure) when be also particularly advantageous.In this case, flexible reservoir 160 and reservoir Content is expanded together and is shunk, so as to prevent due to expansion and contractility and caused possible leakage.

The further feature of reservoir 160 includes that being allowed in the filling moment carries out automatically the ability of particle inspection or existed by patient The ability of particle inspection is carried out using the moment.One or more reservoir barrier portions (such as vault 176) can be by transparent clear Plastic material be molded, this makes it possible to check the material being contained in reservoir.Transparent clearly plastics material Material is preferably cyclic olefine copolymer, it is characterised in that the high grade of transparency and definition, low extract (low extractables), And the biocompatibility with the material being contained in reservoir 160.A kind of suitable material can be from Kentucky State Louis The material of entitled " the BDCCP resins " of the Zeon chemical companies of Wei Er is obtained, and is stepped on by U.S.'s food and FAD It is designated as DMF No.16368.In this applications, reservoir 160 includes that the possibility of minimum hinders the feature for checking (that is, to be allowed in Rotate during inspection).

Passage arm 172 is set to from valve 168 shape of at least one flexible bow-shaped arm for extending to pin manifold or micropin 152 Formula.Bow-shaped arm has the groove 174 for being formed wherein (for example, with reference to Fig. 2).In order to arrange between valve 168 and pin manifold or micro- Fluid path between pin 152,180 covering groove 174 of reservoir arm sealing member.Between reservoir 160 and micropin 152 Fluid path (be arranged in passage arm 172-for example, and shown in Fig. 8) by or phase similar to the material for being used for reservoir 160 above Same material is constituted.For example, passage arm 172 can be by constituting with 160 identical material of vault, and reservoir arm sealing member 180 Can be by constituting with 164 identical material of reservoir arched sealing member.According to one embodiment, two passage arms 172 are both functioned as Fluid path between valve 168 and pin manifold or micropin 152.According to another embodiment, in passage arm 172, only one is used as fluid Path, and remaining passage arm 172 provides structure support.In such an embodiment, groove 174 only will be used as fluid road Pin manifold or micropin 152 are extended fully into from valve 168 in the passage arm 174 in footpath.

Passage arm 172 must be sufficiently flexible bearing activating force.The position of the passage arm 172 in contrast Fig. 2 and Fig. 8, when (it is described in more below) when micropin 152 is driven in patient skin, passage arm 172 is (by reservoir arm sealing member in Fig. 2 180 cover, and for the sake of clarity, reservoir arm sealing member 180 is removed in fig. 8) elastic deformation.During the deformation, lead to Road arm 172 must be maintained between the integrity of the fluid path between valve 168 and pin manifold or micropin 152.In addition, being used for passage The material of arm 172 meets various biocompatibility and storage test.For example, as shown in following table 1, when in infusion device It is tolerant including insulin when, the dominant touch material in reservoir 160 include linear low density polyethylene, cyclic olefine copolymer and Teflon, and can also include transparent clearly plastics.Residual stream between the micropin 152 of reservoir 160 and pin manifold Dominant touch material in dynamic path (passage 62) include COC and/or medical grade acrylic acid, LLDPE, TPE and rustless steel and Pin binding agent.

Table 1

More specifically, micropin 152 can be made up of rustless steel, and pin manifold can be by polyethylene and/or medical grade propylene Acid is constituted.This material is preferably tested by ISO10-993 biocompatibility when the content with reservoir extends and contacts.

Reservoir 160 and passage are optionally allowed and limited to the valve 168 being arranged between reservoir 160 and passage 172 Flow of fluid between 172.Valve 168 is preactivate position (for example, shown in Fig. 2, Fig. 3 and Fig. 6) and activates position (for example, Shown in Fig. 8-Figure 10) between move.When in activation position, valve allows the fluid stream between reservoir 160 and passage 172 Move and thus allow the flow of fluid to pin manifold and micropin 152.

When in use, valve 168 is finally pushed in activation position by the motion of activator appliance button 128, and this is by valve 168 Motion between Fig. 5 and Figure 10 is most preferably illustrated.As shown in Figure 10, the motion of valve 168 makes the enlarged distal tip portion row of valve 168 Enter, so as to allowing medicine from 160 flow channel 172 of reservoir and being downward through fluid path to reach pin manifold.

Above-described embodiment includes at least one pin 152 or micropin 152, but may illustrate comprising some (such as two) Micropin 152.Every micropin 152 is preferably at least 31 dividers (gauge) or less such as 34 dividers, and be anchored at can It is arranged as in the patient's pin manifold with the fluid communication of reservoir 160.Micropin 152 is when infusion device 100 is included more than one Can also have the combination of different length or divider or different length and divider, and one can be included along body length Individual or multiple ports, the port is preferably provided near the needle point of micropin 152 or pinpoint inclined plane is (if arbitrary micropin 152 With one) near.

According to one embodiment, the transfer rate of the reservoir contents of the divider control infusion device 100 of micropin 152. It is defeated when carrying out on longer period period than being generally associated with middle injector injection (needing bigger needle guard or pin) During note, it is practical to convey reservoir contents using multiple 34 dividers 152.In the disclosed embodiment, target can be used It is any micropin 152 of Intradermal or subcutaneous space, but (for example, diagram embodiment includes length between 1mm and 7mm Intradermal micropin 152 4mm).The arrangement of micropin 152 can be linearly or nonlinearly array, and can include such as being answered by specific With required any number of micropin 152.

As described above, micropin 152 is positioned in pin manifold.In pin manifold, every micropin 152 is provided with least one fluid company Path or passage 172.Manifold can only have single path for one or more micropins 152, or can arrange and will store Storage content is dividually routed to multiple fluid paths or passage of every micropin 152.These paths or passage can be with Including the crooked route advanced for content, so as to affect Fluid pressure and transfer rate, and as flow limiter.Position Path or passage in the pin manifold can depend on application and to width, depth and configuration set point, wherein channel width Typically range between 0.015 inch and 0.04 inch, it is therefore preferable to 0.02 inch, and it is dead in manifold to be configured to reduction Angle.

According to one embodiment, reservoir sub-component 120 has a pair of holes 184 and 188 to help reservoir sub-component 120 Position with regard to bottom enclosure 104.First post 192 of bottom enclosure 104 and the second post 196 (being described in more below) are inserted through Corresponding hole 184 and 188.

In the exploded view that reservoir sub-component 120 is removed, Fig. 4, Fig. 7 and Fig. 9 illustrate bottom enclosure 104 includes base This cylindrical shell 200, pressing spring 140 and plunger 144 are arranged in the cylindrical shell 200.According to one embodiment, circle Barrel-type casing 200 includes multiple recess channels 204, multiple with the correspondence for guiding plunger 144 when plunger is moved in housing 200 Lower limb 208 and foot 212.Lower limb 208 and foot 212 collectively form plunger projection 214.For example, as shown in Fig. 4, Fig. 7 and Fig. 9, depression is logical Road 204 extends from the part in the path of the top down of cylindrical shell 200 only along cylindrical shell 200.It is logical in depression Opening 216 is provided with below road 204, the foot 212 of plunger 144 can pass through opening 216 and extend to the outer of cylindrical shell 200 Side.Be open 216 substantially L-shaped, with the horizontal component at the base portion of cylindrical shell 200 and with 204 base of recess channel The vertical portion of this alignment.

When infusion device 100 is in pre-activated state, pressing spring 140 is compressed (for example, such as Fig. 4-Fig. 6 by plunger 144 Shown in), and the foot 212 of plunger 144 be substantially disposed in opening 216 horizontal component in.The power of pressing spring 140 makes plunger 144 foot 212 is biased against the top (for example, the ledge of cylindrical shell 200) of the horizontal component of opening 216.As below In greater detail, pressing spring 140 and plunger 144 form compression system to pressurize when infusion device 100 is activated together Reservoir 160.

As described in more detail below, rotor 136 (for example, is schemed in preactivate position around the base portion of cylindrical shell 200 Illustrate in 2- Fig. 4) rotate between activation position (for example, illustrating in Fig. 8-Figure 10).When rotor 136 is rotated from preactivate position During to activation position, at least one foot engagement pistons 144 engaged with the surface 220 (for example, shown in Fig. 4) of rotor 136 At least one of foot 212 and rotate plunger 144 so that the vertical portion and recess channel of foot 212 and opening 216 204 alignments.At this point, pressing spring 140 makes that plunger 144 is moved up and foot 212 is guided by rising passway 204.

Pressing spring 140 is included in infusion device 100 to apply substantially homogeneous power to reservoir 160, by content Thing is expelled from reservoir 160.Pressing spring 140 is used for storage energy, and which is releasing loose moment pressurizing reservoir when in use 160.Pressing spring 140 is kept under compression by the engagement between the foot 212 and cylindrical shell 200 of plunger 144.This connects Conjunction prevents pressing spring 140 from putting stress upon the film (described below) of reservoir 160 or any remaining dress in memory period Put on part (in addition to bottom enclosure 104 and plunger 144).Plunger 144 is sufficiently rigid to resist spring tension and deformation, and And should not fail under common load.

As described above, when rotor 136 is rotated to activation position from preactivate position, the foot 212 of rotor 136 and plunger 144 At least one of engage, and rotate plunger 144 so that the vertical portion and recess channel 204 of foot 212 and opening 216 Alignment.The pressing spring 140 of compression subsequently moves up plunger 144, and the film of reservoir 160 is exerted a force to for this On.Pressing spring 140 can be configured to preferably produce from about 1psi to the pressure of about 50psi in reservoir 116, and And more preferably from about 2psi to the pressure of about 25psi for reservoir contents intradermal delivery.For percutaneous Injection is transfused, and the scope of about 2psi to about 5psi can be enough.

According to one embodiment, activator appliance button 128 includes patient interface surface 132, and patient urges the surface 132 to swash Infusion device 100 living.Activator appliance button 128 also includes hinge arms 224 and activation arms 228 (for example, figure 3 illustrates).Swash The hinge arms 224 of device button living 128 include the cylindrical portion with opening.Activation arms 228 include raised 230 (for example, with reference to Fig. 3).Include load-bearing surface 232 and be set to the cantilevered end phase with load-bearing surface 232 according to one embodiment, raised 230 Adjacent locking surface 234.According to one embodiment, projection 230 forms acute angle with the major part of activation arms 228.

The first post 192 being arranged in bottom enclosure 104 is upwardly extended from bottom enclosure 104.According to one embodiment (example Such as, as shown in figs. 4 and 7), the base portion of the first post 192 includes a pair of planar sides 236 and a pair circular sides 240.In addition, example Such as, as shown in figs. 4 and 7, the second post 196 and the first and second driving spring base portions 244 and 248 are from bottom enclosure 104 Upwardly extend.As will be described in more detail below, the anchoring of the first and second driving spring base portion 244 and 248 driving spring 148 Corresponding end.First driving spring base portion 244 is set to adjacent with the second post 196 and has space between them.

According to one embodiment, Fig. 3 and Fig. 6 illustrates position of the activator appliance button 128 relative to bottom enclosure 104, with For assembling activator appliance button 128.In the position, the opening of the cylindrical portion of hinge arms 224 enables activator appliance button 128 Level is slided (through planar side 236) and is engaged with the first post 192.Hinge arms 224 (and thus activator appliance button 128) It is then able to rotate around the first post 192.When activation arms 228 are moved between the second post 196 and the first driving spring base portion 244 Space in when, raised at least one of 230 and activation arms 228 elastic deformation, until raised 230 load-bearing surface 232 Cantilevered end is till the holding surface 252 of the second post 196.The cantilevered end movement of raised 230 load-bearing surface 232 Through the holding surface 252 (for example, with reference to Fig. 4) of the second post 196 and raised 230 locking surface 234 and holding surface 252 Audition click sound and touch feedback of the engagement there is provided expression activator appliance button 128 in preactivate position.

Referring back to Fig. 2-Fig. 4, and Fig. 7-Fig. 9, rotor 136 comprises additionally in activation protuberance 256 and driving spring keeps Device 260.When patient urges activator appliance button 128, the activation arms 228 of activator appliance button 128 are connected with activation protuberance 256 Close, so that rotor 136 is rotated to activation position from preactivate position.

When rotor 136 is in preactivate position, driving spring 148 is maintained at preactivate by driving spring keeper 260 In position.It has been observed that the first and second driving spring base portion 244 and 248 anchors the opposite end of driving spring 148.Driving At the approximately mid-point of spring 148, the substantially U-shaped protuberance being provided with as shown in such as Fig. 2 and Fig. 3, for rotor 136 Driving spring keeper 260 is engaged.Therefore, when rotor 136 is in preactivate position and driving spring 148 is protected with driving spring When holder 260 is engaged, driving spring 148 is maintained at extended state.And work as driving spring keeper 260 and release loose driving spring 148 (that is, when rotor is rotated from preactivate position to activation position as shown in such as Fig. 8-Figure 10), driving spring 148 Micropin 152 is driven with (and by the opening in release mechanism 108, hereafter more detailed by opening in bottom enclosure 104 300 It is thin to describe) extend to the outside of infusion device 100.

Thus, as will be described in more detail below, swashing for infusion device 100 is realized with single multi-functional/step process Living and excitation include by patient urge activator appliance button 128, and rotor 136 due to the activation arms 228 in activator appliance button 128 And rotor 136 activation protuberance 256 between engagement and caused rotation.As described above, the rotation of rotor 136 makes plunger 144 rotations and the fluid for releasing loose plunger 144 to pressurize in reservoir 160.In addition, the rotation of rotor 136 is by driving spring 148 release pine from driving spring keeper 260, so as to drive micropin 152 to extend to the outside of infusion device 100.It is single many Function/step process is additionally included in when activator button 128 is urged and makes valve 168 as activator button 128 engages and move valve 168 Motion from from preactivate position to activation position, so as to start stream of the fluid via passage 172 between reservoir and micropin 152 It is dynamic.

As described above, patch-like infusion device 100 also includes release mechanism 108.In order to prevent unintentionally or unexpected needlestick injury, The intentional recycling of anti-locking apparatus and in order to shield exposed pin, is provided with locking pin release mechanism 108.When by infusion device 100 automatically and immediately activate release mechanism 108 when removing from patient skin surface.According to an enforcement being described in more below Example, flexible adhesion pad 264 are attached to the bottom point of bottom enclosure 104 and the bottom point of release mechanism 108.Adhesive pad 264 and trouble Person's skin contacts and keeps infusion device 100 in place on a skin surface during use.For example, as in Figure 11 and Figure 12 Shown, when infusion device 100 is removed from skin surface, release mechanism 108 extends to the position of shielding micropin 152.When complete During full extension, release mechanism 108 locks unexpected injury or exposure in place and that prevent patient's pin 152.

Generally, passive type security system is most desired.This makes device forget to be provided with unexpected situation about removing or patient Can be from protection in the case of security step.Supply as a kind of typical use of this infusion device 100 is to provide usual night The human growth hormone answered, the patient (such as child) therefore, it is possible to desirably dress the device actually can be dressed all night long They, even if expected conveying can be completed within the time less than 10 minutes.In the case of no passive type system, if infusion Device 100 drops, then micropin 152 can be pierced in patient or caretaker's body again.Solution is restriction activity during use Or including passive type security system.

With regard to security system, three options are there may typically be.First option is that pin 152 is retracted in device.Second choosing Item is that shielding pin 152 is close to eliminate, and the 3rd option is to destroy pin 152 and prevent pricking wound.Such as proactive system etc Other systems are using manually shielding and/or destroy, or pressed using other button or pine is manually released in the action that is similar to Security feature.The detailed description of the passive type secured embodiment to the present invention is provided below.

One secured embodiment of the present invention is passive type, the drawer type design embodiments encapsulated completely, such as safe machine Structure 108.Fig. 5, Figure 10 and Figure 12 be a diagram that respectively release mechanism 108 before activation, after activation, and release mechanism The three-dimensional cutaway view of 108 infusion devices 100 after the expansion.

When infusion device 100 is removed from skin, flexible adhesion pad 264 (is attached to the basal surface of bottom enclosure 104 With the basal surface of release mechanism 108) release mechanism 108 will be pulled out and before adhesive pad 264 releases loose skin surface by safety Mechanism 108 locks in place.In other words, the power needed for remove adhesive pad from skin surface is more than 108 institute of expansion release mechanism The power for needing.According to one embodiment, for example, as shown in Figure 13, what release mechanism 108 included contacting with patient skin is flat Surface portion 268.Flat surfaces 268 are in following positions：A part (shown in broken lines in Figure 13) for wherein adhesive pad 264 is attached It is connected to release mechanism 108 so that when infusion device 100 is removed from skin by patient, adhesive pad 264 will work to pacify Full mechanism 108 launches from infusion device 100, so as to shield micropin 152, should otherwise when infusion device 100 is removed from patient Micropin 152 will exposure.When release mechanism 108 is fully extended, release mechanism 108 locks meaning that is in place and preventing micropin 152 Outer injury or exposure.

According to one embodiment, adhesive pad 264 is set to basic two parts, a bottom table for being located at bottom enclosure 104 In the major part in face, and one is located on the basal surface of release mechanism 108.When infusion device 100 is removed, two pasters are only Vertical mobile and release mechanism 108 can be rotated relative to bottom enclosure 104.According to another embodiment, two parts are formed as The flexible adhesion pad 264 of integral type, in the major part of the basal surface that one of part is arranged on bottom enclosure 104, and one Part is arranged on the basal surface of release mechanism 108.

According to one embodiment, release mechanism 108 is metallic stamping pieces.According to another embodiment, release mechanism 108 by with The essentially identical material of bottom enclosure 104 is made.As shown in Figure 14, release mechanism 108 includes front shielding part 272, is arranged on A pair of of the rear portion office of release mechanism 108 insertions are raised 276, be separately positioned on release mechanism 108 marginal portion 284 it is upper A pair of pivot protrusions 280 at rearward end, from the upwardly extending guide post of bottom interior surface of the substantially flat of release mechanism 108 288th, and also from the upwardly extending locking column of the bottom interior surface of release mechanism 108 292.Front shielding part 272 is in marginal portion Extend to make patient shield with micropin 152 when release mechanism 108 is launched on 284.Guide post 288 includes the recess being located therein Protuberance 296 (for example, shown in Fig. 7 and Fig. 9) is kept with the safety when rotor 136 is in preactivate position with rotor 136 Engage, to prevent release mechanism 108 from launching before the activation of infusion device 100.

In addition, as described above, release mechanism 108 includes pin opening 156.Before release mechanism 108 is launched, pin opening 156 The space moved for micropin 152 with offer least partially overlapped with the opening 300 in bottom enclosure 104.Locking column 292 is distinguished It is set to adjacent with the forward edge of pin opening 156.Bottom enclosure 104 includes guide post opening 304 (for example, in Fig. 7 and Fig. 9 It is shown), be set to (for example, illustrate in Fig. 4 with the opposite side edge adjacent pair of bottom enclosure 104 insertion bump openings 308 One of those), and a pair of pivot seat 312 (for example, Fig. 7 and Tu being arranged in the opposite sides of bottom enclosure 104 Shown in 9).

Referring again to Figure 14, insertion raised 276 respectively includes coupling part 316 and extension 320.Implemented according to one Example, rear of the coupling part 316 from the bottom interior surface of release mechanism 108 towards infusion device 100 is with regard to release mechanism 108 Bottom interior surface extend into non-perpendicular angle.Extension 320 is each from extension 320 towards the phase of release mechanism 108 Outside is answered essentially perpendicularly to extend.In order to release mechanism 108 is assembled in bottom enclosure 104, release mechanism 108 is remained With regard to 104 one-tenth about 45 ° of angle of bottom enclosure, and insertion raised 276 is inserted through into insertion bump openings 308.Subsequently Release mechanism 108 is rotated to a position so that guide post 288 is inserted through guide post opening 304, and release mechanism 108 Bottom interior surface be basically parallel to the basal surface of bottom enclosure 104 and contact with the basal surface.

Referring again to Fig. 7 and Fig. 9, although these views illustrate in activation position in rotor 136, Fig. 7 and The resolution characteristic of Fig. 9 is easy to illustrate the stage being assembled into release mechanism 108 in bottom enclosure 104.It is to be understood, however, that It is before activation release mechanism 108 to be assembled in bottom enclosure.As shown in Figure 4, in release mechanism 108 upwards After rotation, release mechanism 108 is moved rearwards by relative to bottom enclosure 104 so that pivot protrusion 280 crosses pivot seat 312 Corresponding leading edge and be arranged on the top for pivoting seat 312, locking column 292 is set to the opening 300 with bottom enclosure 104 Lateral edges it is adjacent, and rotor 136 safety keep protuberance 296 engage with guide post 288.

Figure 14 is back to, each in locking column 292 includes from the flat bottom inner surface of release mechanism 108 hanging down substantially The straight cylindrical extension 324 for extending, and the end that is arranged on cylindrical extension 324 wedge-like portion 328.Work as wedge shape When the height of part 328 increases relative to the bottom interior surface of release mechanism 108, the width increase of wedge-like portion 328.

When release mechanism 108 launches and is rotated down relative to bottom enclosure 104, wedge-like portion 328 is against outside bottom The respective side edge of the opening 180 of shell 104, so as to cause the elastic deformation toward each other of locking column 192.When release mechanism 108 it is complete During full expansion, raised 280 are changed into resting against in pivot seat 312.In addition, the top edge of wedge-like portion 328 is through opening 300 Feather edge, and locking column 292 skips back to its basic undeformed state, so as to provide audition click sound and touch feedback to express Release mechanism 108 is fully expanded and thus micropin 152 is capped.Figure 11 and Figure 12 is back to, once release mechanism 108 is complete It is complete to launch and locking column 292 has skipped back to its basic undeformed state, the top edge of wedge-like portion 328 just with 300 phase of opening Adjacent ground is engaged with the basal surface of bottom enclosure 104, so as to prevent release mechanism 108 from rotating up relative to bottom enclosure 104, And prevent micropin 152 from exposing.In addition, as described above, front shielding part 272 makes patient shield with micropin 152.

Therefore, release mechanism 108 is arranged to the passive type secured embodiment of single-piece, and provides under manpower load not The good locking that can be damaged.Using this passive type release mechanism, during injecting, do not have other power to be applied on skin, And after usage micropin 152 is retained securely in infusion device 100.

After 100 use of infusion device, patient can check again for device to guarantee that whole dosage is conveyed.With regard to this Speech, according to the one embodiment shown in Figure 15 A- Figure 15 D, infusion device 100 includes dosage end indicator (EDI) 124. EDI124 includes 336 He of the first and second arms that main body or post 332 and the top basic horizontal relative to main body 332 extend 340。

EDI124 also includes from the 332 of main body top the spring arm 344 being bent upwards.According to one embodiment, spring Arm 344 is pushed against the bottom side of reservoir sub-component 120, so that EDI124 is towards 104 elastic biasing of bottom enclosure, to guarantee For example during the transport and disposal of infusion device 100, EDI124 will not move freely through out infusion device 100.According to a reality Example is applied, spring arm 344 is pushed against the bottom side of vault 176.

Fig. 4 is back to, is generally vertically moved during main body 332 is arranged on EDI passages 348 and in the channel.According to one Individual embodiment, EDI passages are set to adjacent with the recess channel 204 of the lower limb 208 and foot 212 of guiding plunger 144.The One arm 336 extends across the top of the recess channel 204.

Figure 15 A are back to, vertical extrusion or beacon 352 are upwardly extended from the end of the second arm 340.Will storage when When storage content is exported, beacon 352 extends through EDI 356 (for example, with reference to Figure 15 C) of opening in top casing 116, Dosage is had arrived at expression to terminate.According to one embodiment, EDI124 is formed as one-piece construction.

As shown in Figure 15 B, when plunger 144 after the activation due to pressing spring 140 in cylindrical shell 200 to During upper traveling, in the foot 212 of plunger 144 is contacted with first arm 336 of EDI124.The phase is conveyed in reservoir contents Between, EDI124 liftings upwards so as to overcome the biasing of spring arm 344, and are caused beacon 352 gradually to extend through by foot 212 Cross EDI openings 356.Referring back to Figure 10, when after activation, medicine is just discharged from reservoir 160, beacon 352 is from infusion dress Put 100 partly to extend.Once the conveying of reservoir contents is completed and plunger has been carried out its complete stroke, vertically extrude Part 352 is just fully extended, as shown in Figure 15 D.Thus, EDI124 adopts the linear movement of plunger 144 to produce EDI124 Linear movement, the linear movement of the EDI124 can be visible in the outside of infusion device 100, so as to express reservoir contents Conveying.

Figure 16 A and 16B illustrate another dosage end indicator (EDI) 360 in infusion device 100 and its behaviour Make.As shown in fig. 16, the base portion 364 of the beacon 368 of EDI360 has different face from the remainder of beacon 368 Color.As illustrated in figure 16b, the visible conveying for showing medicine on the outside of infusion device 100 of base portion 364 is substantially finished.At other In aspect, EDI360 is substantially similar with EDI124.

Figure 17 A and 17B illustrate another dosage end indicator (EDI) 372.As shown in figs. 17 a and 17b, EDI372 include main body 376, from main body 376 extend the first arm 380, and also from main body 376 extend first spring arm 384 With second spring arm 388.Additionally, beacon 392 extends from the end of the first arm 380.According to one embodiment, beacon 392 Including base portion 396 and top 400.According to one embodiment, at least a portion of base portion 396 and the remainder of beacon 392 With different colors.In this embodiment, the different colours part of base portion 396 is visible on the outside of infusion device 100 shows medicine The conveying of thing is substantially finished.

As shown in figure 17 a, EDI372 also includes from main body 376 a pair of the stabilizing arm 412 and 416 for extending.Stabilizing arm 412 Stablize EDI372 in EDI372 moving process with 416.Figure 18 illustrates the EDI372 being arranged in infusion device.As in Figure 18 Shown, cylindrical shell 200 includes the passage 420 of the main body 376 for being removably received by EDI372.Stabilizing arm 412 and 416 is contacted The outside of cylindrical shell 200 is with the stable EDI372 in EDI372 moving process.

After the activation, when plunger 144 is advanced in cylindrical shell 200, the contact simultaneously lifting of foot 212 of plunger 144 The main body 376 of EDI372, thus by the conversion of motion of plunger 144 for main body 376 motion and the thus fortune of beacon 392 It is dynamic.

First spring arm 384 and second spring arm 388 be respectively provided be arranged at its each the spring arm post 404 of end, 408.According to one embodiment, the bottom side of the contact reservoir of spring arm post 404 and 408 sub-component 120 so that EDI372 together with Spring arm 384 and 388 is elastically inwards biased relative to top casing 116, to guarantee (such as transporting before dosage terminates During infusion device 100 is disposed) outside EDI372 is not extend to infusion device 100.According to one embodiment, spring arm post 404 and 408 bottom sides for being pushed against vault 176.

When plunger 144 arrives at the terminal of its traveling stroke, pressing spring 140 acts on the power on plunger 144 and overcomes The biasing of one spring arm 384 and second spring arm 388, outside extending to infusion device 100 so as to cause signal post 392 and thus Show that the conveying of medicine is substantially finished.

Figure 19 A and 19B respectively illustrate another dosage end indicator (EDI) 424 and its operation.Such as institute in Figure 19 A Show, EDI424 includes the post 428 with helical form face 432.Arm 436 that EDI424 also includes from the end of post 428 extending, and It is outer that vertical extrusion or beacon 440, the vertical extrusion or beacon 440 extend across top from the end of arm 436 EDI in shell 116 is open 444 (see Figure 20 A) with can be on the outside of the infusion device 100.According to one embodiment, EDI is opened Mouth 444 is arcuate slot.Post 428 is also with for EDI424 to be rotationally attached to the base portion 448 of bottom enclosure 104.

Figure 19 B illustrate the helical form face 432 of the lateral edges of contact plunger 144.Figure 20 A are illustrated in pre-activated state In infusion device 100.According to one embodiment, in the whole motor process of plunger, the helical form face 432 of EDI424 carries Against the edge of plunger 144.Therefore, when plunger 144 is travelled upwardly in cylindrical shell 200 after the activation, plunger 144 Edge and helical form face 432 between contact be led to EDI424 rotate.According to one embodiment, in 144 motor process of plunger Interaction between middle helical form face 432 and the edge of plunger 144 is led to that post 428 rotates the rotation circle complete less than Number.In other words, the pitch in helical form face 432 is led to that post 428 rotates the rotation complete less than in 144 motor process of plunger The number of turns.

When EDI424 rotates, beacon 440 is correspondingly rotated in EDI openings 444.And when beacon 440 is arrived at During the end of EDI openings 444, as illustrated in figure 2 ob, EDI424 indicates that the conveying of medicine is substantially finished.

Another dosage end indicator (EDI) 452 and its behaviour are illustrated similar to Figure 19 A and 19B, Figure 21 A and 21B Make.As shown in figure 21 a, EDI452 includes the post 456 with helical form face 460.Additionally, post 428 is with for by EDI452 It is rotationally attached to the base portion 462 of bottom enclosure 104.EDI452 is additionally included in the signal indicator 464 at the top of which, signal Indicator 464 can be by being open 468 (see Figure 22 A) on the outside of the infusion device 100 in the EDI in top casing 116.

Figure 21 B illustrate the helical form face 460 of the lateral edges of contact plunger 144.Figure 22 A are illustrated in pre-activated state In infusion device 100.According to one embodiment, in the whole motor process of plunger, the helical form face 432 of EDI424 carries and supports By the edge of plunger 144.Therefore, when plunger 144 is travelled upwardly in cylindrical shell 200 after the activation, plunger 144 Contact between edge and helical form face 460 causes EDI424 to rotate.Compared with the EDI424 of Figure 19 A, helical form face 460 has Finer pitch.Therefore, EDI452 is rotatably more in plunger 144 and EDI424 stroke procedures.According to one embodiment, Interaction in 144 motor process of plunger between the edge of helical form face 460 and plunger 144 is led to that post 456 rotates at least One complete rotating cycle.In other words, the pitch in helical form face 460 be led to 144 motor process center pillar 456 of plunger rotate to A few complete rotating cycle.According to one embodiment, EDI452 rotate in the stroke procedure of plunger 144 one it is complete Whole rotating cycle.

According to one embodiment, signal indicator 464 is such as arrow.Correspondingly, with EDI be open 468 adjacent tops There is at least one labelling 472 on the exterior section of portion's shell 116.When EDI452 is open in EDI due to the stroke of plunger 144 In 468 during rotation, thus signal indicator 464 can refer on the outside of the infusion device 100 relative to the rotation of labelling 472 Show the process of drug delivery.

According to one embodiment, the pitch in helical form face 460 is defined as being led to stroke procedure of the post 456 in plunger 144 Just complete less than two rotating cycle of middle rotation.Therefore, as shown in Figure 22 B, in just complete less than 2 rotation of advancing Turn-take after number, EDI452 indicates that the conveying of medicine is substantially finished.

As shown in Figure 23 A-23C, the various labellings adjacent with the EDI openings in top casing 116 can be adopted to refer to Show the process of drug delivery.For example, Figure 23 A illustrate labelling 476, and shown labelling 476 includes the scale with scale.It is this The labelling 476 for matching that is open with arch EDI can be together adopted with EDI424.But as a rule will be understood that, it is various Labelling can also be open with variously-shaped EDI and various EDI embodiments are together adopted.

Figure 23 B illustrate labelling 480, and the labelling 480 includes the symbol of the expanded state for representing reservoir 160.For example, One symbol indicates that reservoir 160 is substantially saturated with, and intermediate symbols indicate that reservoir 160 is substantially saturated with half and therefore medicine The conveying of thing is substantially finished half, and the 3rd symbol indicate reservoir 160 be substantially it is empty and therefore medicine it is defeated Send and be substantially finished.

Figure 23 C illustrate labelling 484, and depending on the direction of rotation of corresponding EDI, the labelling 484 includes representing storage The fraction symbol of the fraction of the expanded state of storage 160 or the drug delivery for completing.For example, if having arrow signal indicator The EDI that turns clockwise together adopt with labelling 484, then the motion of the EDI will indicate reservoir 160 expanded state.On the contrary Ground, if rotate counterclockwise EDI with arrow signal indicator is together adopted with labelling 484, the motion of the EDI will be indicated The fraction of the drug delivery for having completed.

Figure 24 A and 24B illustrate another dosage end indicator (EDI) 488 and its operation.According to one embodiment, EDI488 is Pressure Sensitive Tape 488.When plunger 144 arrives at the terminal of its traveling stroke, the pressure of plunger 144 is (due to pressing spring 140 power) it is given to Pressure Sensitive Tape 488.Pressure against Pressure Sensitive Tape 488 is led to color change, thereby indicate that drug delivery is basic On complete.Because the top of reservoir (such as the window being placed in one) is transparent, color change is visible.

According to one embodiment, EDI488 is arranged in reservoir 160, such as in the interior surface of transparent vault 176. In the destination county of the traveling stroke of plunger 144, the pressure against the plunger 144 of reservoir arched sealing member 164 is stored for device arch Shape sealing member 164 is transferred to Pressure Sensitive Tape 488, so as to be led to its color change.

Figure 24 A and 25A illustrate the infusion device 100 in pre-activated state.According to as shown in Figure 24 A and 25A One embodiment, EDI488 is arranged at the sheet of infusion device 100 in vivo with can be from can from the outside of infusion device 100 See.Additionally, EDI488 is arranged so that when plunger 144 arrives at the terminal of its traveling stroke, the foot 212 of plunger 144 is due to adding The power of pressing spring 140 and contact Pressure Sensitive Tape 488, and the pressure against the foot 212 of Pressure Sensitive Tape 488 is led to the face of Pressure Sensitive Tape 488 Color change.Figure 24 B and 25B are illustrated to contact Pressure Sensitive Tape 488 and be led to color change in foot 212 and are completed so as to indicate drug delivery Infusion device 100.

Figure 26 A and 26B illustrate another dosage end indicator (EDI) 492 and its operation.According to one embodiment, EDI492 is the dyestuff bag with least two detached chambers 496 and 500.When plunger 144 arrives at the terminal of its traveling stroke When, the pressure (due to the power of pressing spring 140) of plunger 144 is given to dyestuff bag 492 so that two chambers 496 and 500 it Between separator 504 rupture.Once separator 504 is broken, the content of two chambers 496 and 500 mixes and mixture Change color, thereby indicate that drug delivery is substantially finished.

According to one embodiment, chamber 496 has yellow dye and chamber 500 has blue dyestuff.Once separator 504 breaks Split, blue dyestuff and yellow dye mix and formed green dye, so as to indicate that drug delivery is substantially finished.

According to one embodiment, EDI492 is arranged in reservoir 160, such as on the inner surface of transparent vault 176. The destination county of the traveling stroke of plunger 144, the pressure against the plunger 144 of reservoir arched sealing member 164 are stored for device arch Sealing member 164 is transferred to dyestuff bag 492, so as to be led to its color change.

Figure 26 A and 27A illustrate the infusion device 100 in pre-activated state.According to as shown in Figure 26 A and 27A One embodiment, EDI492 is arranged at the sheet of infusion device 100 in vivo with can be from can from the outside of infusion device 100 See.Additionally, EDI492 is arranged so that when plunger 144 arrives at the terminal of its traveling stroke, the foot 212 of plunger 144 is due to adding The power of pressing spring 140 and contact dyestuff bag 492, and the pressure against the foot 212 of dyestuff bag 492 makes separator 504 rupture simultaneously And it is led to the color change of dyestuff bag.Figure 26 B and 27B illustrate in the contact of foot 212 dyestuff bag 492 and be led to color change so as to Indicate the infusion device 100 that drug delivery is completed.

Figure 28 illustrates the embodiment of the infusion device 700 with injection port 704.Injection port is provided to emptying or portion Divide being close to for the reservoir 708 filled so that the combination of material or material can be injected into reservoir by patient before activation It is interior.Alternatively, the group that pharmaceutical production person or pharmacists can adopt injection port 704 to use material or material before being sold Close filling infusion device 700.Nearly all in terms of other, infusion device 700 is similar to previously described infusion device 100.

The operation of infusion device 100 will now be described.The above embodiment of the present invention preferably includes button, and (activator appliance is pressed 128) button designs, wherein, infusion device 100 can position and be attached to skin surface, and by urging activator appliance button 128 And energized and/or activation.More specifically, in first step, patient from moving-out device in aseptic packaging (not shown), remove it is viscous Close the lid (not shown) of pad 264.Patient also removes needle cover 112.When infusion device 100 is removed from the package and using it Before (for example, with reference to Fig. 1, Fig. 2, Fig. 4 and Fig. 5), the infusion device 100 in pre-activated state enable the patient to check device and Content therein, including check lose or damage part, the Expiration Date, the medicament of atomization or color offset, etc..

Next step is that infusion device 100 is positioned and is applied on the skin surface of patient.As patche, patient Infusion device 100 is compeled to be pressed on skin securely.The side of adhesive pad 264 is attached to the basal surface and peace of bottom enclosure 104 The basal surface of full mechanism 108, and infusion device 100 is fixed to the skin of patient for the opposition side of adhesive pad 264.These (bottoms Shell 104 and release mechanism 108) basal surface can be flat, curve or shape in any suitable manner, and And adhesive pad 264 is fixed on these basal surfaces.According to one embodiment, before transportation, the lid (such as film) of adhesive pad 264 It is applied on the patient-side of adhesive pad 264, to protect bonding part during transportation.As described above, before the use, patient is peeled off Adhesive cover, so that adhesive pad 264 is exposed for arranging against skin.

After adhesive cover is removed, infusion device 100 can be arranged by patient against skin, and urge to guarantee suitably Attachment.As described above, once appropriate position, just the device is activated by urging activator appliance button 128.The activation step releases pine Plunger 144 and pressing spring 140, so that plunger 144 can be urged against the flexible membrane of reservoir 160, and (reservoir arch is close Sealing 164), so as to pressurizing reservoir.The activation step is additionally operable to driving spring 148 is kept from the driving spring of rotor 136 Device 260 releases pine, (is opened by the pin of opening 300 and release mechanism 108 in bottom enclosure 104 with extending so as to drive micropin 152 Mouth 156) to infusion device 100 outside and micropin 152 rested in patient's body.In addition, activation step makes 168 dozens, valve Open, so as to set up the fluid communication road between reservoir 160 and micropin 152 via passage 172 (for example, with reference to Fig. 8-Figure 10) Footpath.Significant benefit stems from realizes the ability of each in these actions with single button operation.In addition, another significant Benefit is included using the continuous fluid communication path being entirely included in reservoir sub-component 120.

Once being activated, patient is typically interior by infusion device in a period of time (such as ten minutes to 72 hours) 100 retain completely conveying of the in place or object wearing device for reservoir contents.Drug delivery is basically completed by EDI (examples Such as, EDI124) indicate.Patient is subsequently removed with drop device without with the following skin of destruction or tissue.When deliberately or When surprisingly removing, one or more security features launch to shield exposed micropin 152.More specifically, when infusion device 100 by When patient is removed from skin, adhesive pad 264 makes release mechanism 108 launch from infusion device 100, so as to shield micropin 152, Otherwise when infusion device 100 is removed from patient, micropin 152 can expose.When release mechanism 108 is fully extended, safe machine Structure 108 locks unexpected injury or exposure in place and that prevent micropin 152.But, if security feature can be configured to activation Device button 128 is not yet urged and micropin 152 not yet extends, and is not launched, so as to before preventing use, release mechanism launches. After use, patient can check again for device to guarantee that whole dosage is conveyed.For example, patient can pass through transparent vault The inside of 176 observation reservoirs and/or inspection EDI124.

The embodiment is suitable for patient and especially human patientses implement many kinds of substance, including medicine and medicine With agent.As used herein, medicinal agent include being carried through body film and surface and in particular skin with biological activity Material.The example enumerated in further detail below includes antibiotic, antiviral agent, analgesics, anesthetis, fenisorex, arthritiss Medicine, antidepressants, antihistaminic, antibiotic medicine, antineoplastic agent, vaccine (including DNA vaccination) etc..Can be to patient's Intradermal or subcutaneous Other materials of conveying include human growth hormone, insulin, albumen, polypeptide and its fragment.Albumen and polypeptide can be nature What occurring, synthesis or restructuring was produced.In addition, the device can be used in cell therapy, such as in the Intradermal of dendritic cell During infusion.Other materials for being capable of the method according to the invention conveying can be from by preventing, diagnosing, mitigating, treating or controlling Choose in the group of the compositions such as medicine, vaccine more used in disease, wherein, medicine includes：α -1 antitrypsins, anti-angiogenic life It is patent medicine, antisense, butorphanol, calcitonin and the like, Ceredase, II inhibitor of COX-, Dermatological Agentses, dihydroergotamine, many Bar amine receptor agonist and antagonist, enkephalin and other opioid peptide, epidermal growth factor, erythropoietin and similar Thing, follicule-stimulating hormone (FSH), G-CSF, glucagon, GM-CSF, granisetron, growth hormone and the like (include growth hormone Releasing hormone), growth hormone receptor antagonist, hirudin and hirudin analog (such as HIRULOG), IgE inhibitor, islets of langerhans Element, pancreotropic hormone and the like, insulin-like growth factor, interferon, interleukin, sharp lutein, human luteinizing hormone Releasing hormone and the like, low molecular weight heparin, M-CSF, metoclopramide, Midazolam, monoclonal antibody, narcosis analgesic, Nicotine, non-steroidal anti-inflammatory drug, oligosaccharide, ondansetron, parathyroid hormone and the like, parathyroid hormone receptor are short of money Anti-agent, prostaglandin antagonistses, prostaglandin, recombinant soluble receptor, scopolamine, hydroxytryptamine agonist and antagonist, sulphur Acyl pyrimidine benzene, terbutaline, thrombolytics, histoplasmosis activator, TNF and TNF- antagonisies；Vaccine, with or without load Body/adjuvant, including to following related preventative and therapeutic antigens (including but not limited to protein subunit, polypeptide and polysaccharide, many Sugared conjugate, toxoid, based on the vaccine of gene, attenuated live vaccine, reassortant vaccine, deactivation vaccine, full cell, virus and Bacteria carrier)：Addicted, arthritis, cholera, cocaine addiction, diphtheria, tetanus, HIB, Lyme disease, meningitiss, measles, the parotid gland Inflammation, rubella, chickenpox, yellow fever, respiratory syncytial virus, tick-borne Japanese encephalitiss, streptococcus pneumoniae, streptococcus, typhoid fever, stream Sense, hepatitis (including A types, Type B, c-type and E type hepatitis), otitis media, rabies, polioencephalitiss, HIV, parainfluenza viruses, colyliform Virus, Epstein-Barr virus, CMV, chlamydia, typeable haemophiluss, moraxelle catarrhalises, human papilloma virus, pulmonary tuberculosis (include BCG), gonorrhea, asthma, arteriosclerosis, malaria, escherichia coli, senile dementia, helicobacter pylori, Salmonella, sugar Urine disease, cancer, herpes simplex virus, human papilloma and other similar substances, including other things of all primary treatments Matter, such as common cold drug, drug-breaking medicine, antiallergic agent, Bendectin, antiadipositas drug, anti-osteoporotic, anti-infective, analgesia Medicine, anesthetics, fenisorex, anti-arthritic, anti-asthmatic, anticonvulsant, antidepressants, antidiabetic drug, antihistaminic, antiinflammatory Medicine, antimigraine, anti-motion sickness medicine, Bendectin, antineoplastic agent, anti-Parkinson syndrome medicine, antipruritic, psychosiss, solution The medicine of a warm nature, anticholinergic agent, benzodiazepine receptors antagonist, vasodilation (include general blood vessel, coronary artery, external perihaemal canal and Cerebrovascular), osteo stimulative agent, central nervous system stimulant, hormone, sleeping pill, immunosuppressant, muscle relaxant, parasympathetic Nerve block medicine, parasympathomimetic agent, prostaglandin, albumen, peptide, polypeptide and other macromole, analeptic, tranquilizer, property Hypofunction and tranquilizer and Main Diagnosis are for example such as in the United States Patent (USP) of entitled " methods of intradermally injecting substances " No.6, the tuberculin described in 569,143 and other allergy medicaments, the full content of the patent are clear and definite by way of reference It is expressly incorporated herein.

The vaccine formulation for being capable of system and a method according to the invention conveying can be from by can eliminate to human body cause of disease Choose in the group constituted by the antigen or antigenic component of immune response, the antigen or antigenic component stem from HIV-1 and (for example break wound Wind antitoxin, nef, gp120 or gp160), nerpes vinrus hominises (HSV) (such as gD or derivatives thereof, or early protein immediately For example originating from the ICP27 of HSV1 or HSV2), cytomegalovirus (CMV (espespecially people) (such as gB or derivatives thereof), colyliform Virus (include active attenuated virus), Epstein-Barr virus (such as gp350 or derivatives thereof), varicella zoster virus (VZV, for example GpI, II and IE63) or stem from hepatitis viruss (such as hepatitis virus B (such as HbsAg or derivatives thereof), Hepatitis A virus (HAV), hepatitis C virus and E Hepatitis virus)；Or stem from other viral pathogens such as hepatitis viruss Paramyxovirus：Respiratory syncytial virus (RSV, such as F and G-protein or derivatives thereof), parainfluenza viruses, Measles viruss, the parotid gland Scorching virus, human papilloma virus (HPV, such as HPV6, HPV11, HPV16, HPV18), banzi virus (for example, yellow fever virus, Dengue virus, tick-brone encephalitis virus, Japanese encephalitis viruses) or influenza virus (full activity or inactivation of viruses, cracking influenza virus (in ovum or mdck cell grow), or full influenza virus particles or its purification or recombiant protein (such as HA, NP, NA or M albumen or its combination))；Or stem from bacterial pathogen, such as neisseria, including Diplococcus gonorrhoeae and meningitiss Neisser Bacterium (match somebody with somebody by such as capsular polysaccharide and its conjugate, transferrin binding protein, newborn iron-binding protein, PiLC, bacterial cell surface Base)；Micrococcus scarlatinae (such as M albumen or its fragment, C5A protease, lipoteichoic acid), streptococcus agalactiae, Streptococcus mutans； Haemophilus ducreyi；Moraxella, including mucositiss Morakot this Salmonella, also referred to as branhamella catarrhalis (for example, the adhesins and invasion of high molecular and low-molecular-weight)；Bordetella, including bacillus pertussis (such as pertactin, pertussis toxin, PT or derivatives thereof, filamentous hemagglutinin, adenyl cyclase, pili), secondary hundred Day coughs Bordetella and bordetella bronchiseptica；Mycobacterium, including mycobacterium tuberculosis (such as ESAT6, Antigen 85A, 85B or 85C), Mycobacterium bovis, Mycobacterium leprae, shame dirt paratuberculosiss mycobacteria, mycobacterium paratuberculosises, Smegma bacillus；Legionnella, including legionella pneumophilia；Escherichia, including escherichia coli (such as colonization factor, Heat strangles toxin or derivatives thereof, heat-stable toxin or derivatives thereof), enterohemorrhagic Escherichia coli, enteropathogenic E.Coli (example Toxin toxoid or derivatives thereof is congratulated such as)；Vibrio, including vibrio cholera (such as cholera toxin or derivatives thereof)；Will Hayes Bacillus, including Shigella sonnei, dysentery bacterium, Shigella flexneri；Yersinia's genuses, including Yersinia enterocolitica (such as firelight or sunlight albumen), bacillus pestis, artificial tuberculosis yersinia genus；Campylobacter, including campylobacter jejuni is (such as toxin, thin Bacterium cell surface ligand and invasion) and campylobacter coli；Salmonella belongs to, husky including Salmonella typhi, paratyphoid A Door bacterium, Salmonella choleraesuis, Salmonella enteritidis；Listeria, including Listeria monoeytogenes；Helicobacter, Including helicobacter pylori (such as urase, catalase, VacA)；Rhodopseudomonass, including bacillus pyocyaneus；Fructus Vitis viniferae ball Pseudomonas, including staphylococcus aureuses, staphylococcus epidermidiss；Enterococcus, including enterococcus faecalis, enterococcus faecalis；Fusobacterium, bag Include clostridium tetani (such as tetanus toxin and its derivant), bacillus botulinuss (such as Botulinum toxin and its derivant), Clostridium difficile (for example, clostridial toxins A or B and its derivant)；Bacillus, including Bacillus anthraciss (such as botulinum toxin and its derivant)；Corynebacterium, including diphtheria corynebacterium (such as diphtheria toxin, diphtherotoxin and its derivant)；Bao Rou Family name's Spirochaetess, including Bai Shi Borrelias (such as OspA, OspC, DbpA, DbpB), Borrelia garinii are (for example OspA, OspC, DbpA, DbpB), A Fuxini burgdorferis (such as OspA, OspC, DbpA, DbpB), Anderson burgdorferi (such as OspA, OspC, DbpA, DbpB), borrelia hermsii；Ehrlichia, including Ehrlichia equi and human granular leukocyte Property Paul Ehrlich body disease medicament；Rickettsiae, including rickettsia rickettsii；Chlamydiaceae, including chlamydia trachomatiss are (for example MOMP, hepatic binding protein (HBP)), Chlamydia pneumoniae (such as MOMP, hepatic binding protein (HBP)), chlamydia psittaci；Leptospira Category, including leptospria interrogans；Close rotation body category, including Treponoma palladium (for example, rare outer membrane protein), the close spiral shell of tooth dirt Rotation body, treponema hyodysenteriae；Or stem from parasite, such as Plasmodium, including plasmodium falciparum；Toxoplasma, Including toxoplasma gondii (such as SAG2, SAG3, Tg34)；Entamoeba, including Entamoeba histolytica；Babesia, including Babesia microti；Trypanosoma, including schizotrypanum cruzi；Giardia, including Giardia lamblia；Leishmania, including it is large Big leishmania；Pneumocystis, including pneumocystis pneumoniae；Trichomonass, including trichomonal vaginitis；Schistosomicide, including Man Schistosomicide；Or stem from yeast, such as Candida, including Candida albicans；Cryptococcuses, including cryptococcus；As Announce described in No.WO02/083214 in the PCT Patent Application of entitled " vaccine delivery system ", in the whole of this application Appearance is expressly incorporated herein by way of reference.

These also include for phthisical other preferred specific antigens, such as Tb Ral2, Tb H9, Tb Ra35, Tb38-1, Erd14, DPV, MT1, MSL, mTTC2 and hTCC1.Also include fusion protein and its mutation for phthisical albumen, Wherein phthisical at least two, preferred three peptide fusions are bigger albumen.Preferred fusion includes Ra12-TbH9- Ra35、Erd14-DPV-MT1、DPV-MT1-MSL、Erdl4-DPV-MT1-MSL-mTCC2、Erd14-DPV-MT1-MSL、DPV- MT1-MSL-mTCC2, TbH9-DPV-MT1.Most preferably include such as high-molecular-weight protein for chlamydial antigen (HWMP), ORF3 and hypothesis memebrane protein (Pmps).Preferred bacterial vaccine includes stemming from the antigen of Streptococcus, including lung Scorching streptococcus (such as capsular polysaccharide antigen and its conjugate, PsaA, PspA, streptolysin, choline binding protein) and egg White antigen Pneumolysin (Biochem Biophys Acta, 1989,67,1007；Rubins et al., Microbial Pathogeneisi, 25,337-342 (biochemistry and biophysicss document, 1989,67,1007；Lu Bin etc., Microorganism pathogeny, page 25,337-342)), and its mutation detoxified derivaties thereof.Other preferred bacterial vaccines include being derived from It is thermophilic in the antigen of haemophiluss, including Type B hemophilus influenza (" Hib ", such as PRP and its conjugate), typeable influenza Blood bacillus (such as OMP26, high molecular bacterial cell surface adhesins, P5, P6, D albumen and L lipoproteins), And fimbrin and fimbrin derivant peptide or its multiple copy mutation or fusion protein.HbsAg spreads out Biology is well known in the art, and including PreS1, PreS2S antigen etc..It is in a preferred aspect, of the invention Vaccine formulation includes HIV-1 antigens, gp120, particularly when expressing in Chinese hamster ovary celI.In a further embodiment, the present invention Vaccine formulation include gD2t as defined above.

In addition to conveying material listed above, infusion device 100 also can be used in extracting material, Huo Zhejian from patient Control material level in patients.The example of the material that can be monitored or extract includes blood, interstitial fluid or slurry.Taken out The material for taking subsequently can be with analyzed for analyte, glucose, medicine etc..

Although some example embodiments of the present invention are described in detail above, those skilled in the art will hold Readily understood, many modifications are possible new teaching and advantage without substantially deviateing the present invention in the exemplary embodiment. Therefore, all these modifications mean and are included in the range of claims and its equivalent.

Claims (9)

1. a kind of medicament delivery device, including：

Body, the body have the reservoir being arranged in the body for accommodating medicine；

Injection needle, the injection needle are used for the skin for being pierced into patient, and the pin is connected with the reservoir fluid；

Presser unit and plunger, the plunger can in the presence of the power of the presser unit described in vivo it is mobile with In the contact reservoir；And

Pointer device, the pointer device are visible for indicating that drug delivery is substantially finished from the outside of described device, The motion-activated described pointer device of wherein described plunger, and wherein described pointer device by the motion of the plunger turn Turn to the motion of the visible pointer device from the outside of described device；

Wherein, the pointer device includes：

Main body；And

Beacon, the beacon are connected to the main body；

Wherein, when the plunger arrives at the terminal of its traveling stroke, the plunger contacts the pointer device, institute for the first time It is what is caused due to the power of the presser unit to state contact；

Wherein, the pressure against the plunger of dosage end indicator is led to that the beacon is extended on the outside of described device.

2. device according to claim 1, wherein, the base portion of the beacon includes the remainder with the beacon Different colors, thus shows drug delivery substantially when the color of the base portion of the beacon is visible from the outside of described device Complete.

3. device according to claim 1, wherein the pointer device also includes：

First arm and the second arm, first arm and the second arm extend from the first end of the main body；And

Spring arm, the spring arm extend from the first end of the main body；

Wherein described beacon extends from the end of second arm.

4. device according to claim 1, wherein the pointer device also includes：

At least one stabilizing arm, at least one stabilizing arm extend for moving in the pointer device from the body During stablize the pointer device；And

First arm, first arm extend from the main body；

Wherein described beacon extends from the end of first arm.

5. device according to claim 3, wherein:

The plunger includes that from its edge the plunger for extending is raised；And

First arm described in the plunger projection contacts is with by motion that the conversion of motion of the plunger is the beacon.

6. device according to claim 3, wherein：

The reservoir includes the reservoir arched sealing member of vault and flexible on-expansible；

Vault described in the spring arm contact with by the dosage end indicator towards preactivate location bias；And

When the plunger arrives at the terminal of its traveling stroke, the power of the presser unit overcomes the biasing of the spring arm, from And it is led to that the beacon is extended on the outside of described device.

7. device according to claim 1, wherein:

The body includes cylindrical shell, and the plunger is moved in the cylindrical shell；And

The cylindrical shell includes the passage of the main body for being removably received by the dosage end indicator.

8. device according to claim 6, wherein：

The dosage end indicator also includes at least one spring arm, and the spring arm is with the spring arm extended from its end Post；

In the beacon motor process, the spring arm post contacts the vault with by the dosage end indicator direction Preactivate location bias；And

When the plunger arrives at the terminal of its traveling stroke, the power of the presser unit overcomes the biasing of the spring arm, from And it is led to that the beacon is extended on the outside of described device.

9. device according to claim 4, wherein：

The body includes cylindrical shell, and the plunger is moved in the cylindrical shell；

The cylindrical shell includes the passage of the main body for being removably received by the dosage end indicator；And

Described in described at least one stable arm contact, the outside of cylindrical shell is in dosage end indicator movement During stablize the dosage end indicator.