CN104353151B - Injection device - Google Patents

Abstract

A kind of device (100), for conducting drugs to patient's body by being injected into patient skin or being injected through patient skin, described device includes described device：Ontology (104,116), the ontology, which has, to be disposed therein for accommodating the reservoir (160) of drug；Injection needle (152), the injection needle are used to be pierced into the skin of patient, and the needle (152) has inner cavity and is connected to the reservoir (160)；And compression system, the compression system is for the reservoir (160) that pressurizes.Described device further includes pointer device (124), and the pointer device is visible on the outside of described device (100) to be substantially finished for instruction drug conveying.

Description

Injection device

This divisional application is to be 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, with improved patient convenience, ease for use and effect Rate.The present invention further relates to a kind of patch shape, can be used in from holding type substance infusion or injection device, described device on the whole Many kinds of substance or drug are conveyed to patient.More particularly it relates to which a kind of patch shape with dosage end indicator is defeated Note or injection device.

Background technology

A large amount of people's (such as being subjected to the people of such as diabetes etc situation) use certain of such as daily infusion of insulin etc The infusion of therapeutic of kind form, to maintain the tight control to its blood glucose level.Currently, in infusion of insulin treats example, deposit In the Main Patterns of two kinds of daily insulin therapies.First mode includes syringe and novopen.These devices use simple And cost is relatively low, but they need needle to prick in per injection, generally three times a day to four times.Second mode includes infusion pump Treatment, this needs to buy the expensive pump for continuing about three years.The high cost of pump (is about the 8 of the daily rate of syringe treatment Times to 10 times) and finite lifetime be the high obstruction of this treatment.Insulin pump also represents older technology and using cumbersome.This Outside, from the perspective of life style, pump is connected to the pipe fitting in the delivery site of patient abdomen and (is known as " infusion set Group ") it is very inconvenient, and pump heavier so that carrying pump becomes burden.But from the perspective of patient, use It is most preferably in its remaining years reservation pump in the patient of pump.This is because infusion pump is although more more complicated than syringe and pen The advantages of being arranged there is provided the continuous infusion of insulin, exact dose and programmable movement schedule.This leads to closer blood Sugar control and improved health perception.

In view of the growth of observed pump treatment and the number injected daily increase, for better healing interest just Increasing.In the infusion example and similar infusion example, fully meeting the increase interest, to be desirable for following insulin defeated It 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) is combined, and also avoids respective disadvantage.

Several trials have been carried out to provide low cost and free-standing easy to use or " wearable " infusion of drug Device.Some in these devices mean partially or completely droppable.Theoretically, such device is capable of providing infusion The lot of advantages of pump is without thing followed cost and inconvenience.But unfortunately, many by following scarce in these devices Point：Discomfort (by the divider and/or length of used injection needle), conveyed substance including patient in infusion device Between the material used in construction compatibility and interaction and do not activated correctly (for example, due to device by patient Caused by premature activation " wet type " inject) in the case of possible failure.Also it has encountered during manufacturing and in control needle Penetration depth in difficulty, especially when using the injection needle of short and/or fine divider.Pair connect with used device The possibility of the needlestick injury of tactile personnel is also always a problem.

Accordingly, there exist the demands of the substitute to current infusion device (such as infusion pump for insulin), into one The use that step provides the simplicity of manufacture and applied for insulin and non-insulin improves.

Invention content

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

Above-mentioned and/or other aspects of the present invention are realized by providing following apparatus：Described device is for passing through injection It in patient skin or is injected through patient skin and conducts drugs to patient's body, described device includes：Ontology, described There is body reservoir, the reservoir to be arranged in the ontology to accommodate drug；Injection needle, the injection needle is for piercing Enter the skin of patient, the needle set has inner cavity and is connected to the reservoir；And compression system, the compression system are used for Pressurize the reservoir.Described device further include can on the outside of device it is visible be used to indicate drug conveying be substantially finished Pointer device.

Above-mentioned and/or other aspects of the present invention are realized by providing following apparatus：Described device is for passing through injection It in patient skin or is injected through patient skin and conducts drugs to patient's body, described device includes：Ontology；Storage Device, the reservoir are arranged in the ontology to accommodate drug；Injection needle, the injection needle are used to be pierced into the skin of patient The drug of skin and implementation from reservoir；And compression system, the compression system is for the reservoir that pressurizes.The dress Set further includes that can convey the dosage end indicator being substantially finished by the visible drug that is used to indicate on the outside of device.

Other and/or other aspects and advantage of the present invention will be illustrated partly in the following description, and will be from froming the perspective of Bright middle part apparent, or practice through the invention and be appreciated that.

Description of the drawings

From detailed description with reference to the accompanying drawings, above-mentioned and/or other aspects and advantage of the embodiment of the present invention will more It is readily appreciated that, wherein：

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

The infusion device that Fig. 2 illustrates Fig. 1 is in partial exploded view under pre-activated state；

The infusion device that Fig. 3 illustrates Fig. 1 is in partial exploded view under pre-activated state, and wherein activator appliance button is unscrewed To show more details；

The infusion device that Fig. 4 illustrates Fig. 1 is in more complete exploded view under pre-activated state；

The infusion device that Fig. 5 illustrates Fig. 1 is in sectional view under pre-activated state；

The infusion device that Fig. 6 illustrates Fig. 1 is in sectional view under pre-activated state, and wherein activator appliance button is unscrewed；

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

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

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

Figure 10 illustrates the sectional view of the infusion device of Fig. 1 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 bottom 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 for Figure 17 A being set 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 illustrate the embodiment for the label for being used to indicate drug conveying 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 implementation mode

The embodiment of the present invention is reference will now be made in detail to now, example illustration of the invention is in the accompanying drawings, wherein identical attached drawing Label always shows identical element.The embodiment makes the present invention instantiating by referring to accompanying drawing.

The embodiment of present invention described below can be used as convenient, patch-like infusion or injection device 100 with It is in a period of time or disposable fully to the substance of patient's conveying predicted dose, such as liquid medicine or medicament.The device is excellent Selection of land is supplied to end user with pre-filled state (i.e. drug or medicament has been positioned in the reservoir of device).Although herein The patch-like infusion or injection device 100 (for example, shown in Fig. 1) can be used by patient and/or caretaker, still For convenience, the user of the device is hereinafter referred to as " patient ".In addition, for convenience, such as "vertical" and "horizontal" and " top The term of portion " and " bottom " etc is used to indicate about the relative direction that infusion device 100 on a horizontal surface is arranged.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 Outside, the replacement of term " infusion device " and " injection device " is not intended as limiting using to describe to implement the device of the invention Property.Without being fallen within the scope of the present invention from the infusion device of injectability, the injection device of continuous infusion is not executed It falls within the scope of the present invention.For convenience, but without limitation, term " infusion device " is used in the following description.

The patch-like infusion device 100 of Fig. 1 is from holding type and viscous by what is be arranged on the bottom surface of infusion device 100 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 in the flexible reservoir of loose spring effect in the device can be used in passing through one or more patient's needles via needle manifold (for example, micropin) empties the content of reservoir.Substance in reservoir is then defeated by the micropin being driven in skin It send across patient skin.It should be understood that other embodiment is possible, wherein spring is replaced by different types of energy storage dress It sets, these energy storage devices substantially can be mechanical, electronics and/or chemical.

As will be determined by the skilled person understood, there is construct and use patch-like infusion device disclosed herein 100 number of ways.Although the embodiment and following explanation described in reference to the accompanying drawings, embodiment disclosed herein is simultaneously It is non-to mean that limit various optional designs and implements example by what the disclosed invention included.In each open embodiment, the device quilt Referred to as infusion device, but the device also can be with very much (big preparations) faster than the rate usually realized by typical infusion device Rate injection mass.For example, content can be as short as several seconds or conveyed in the long period to 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 and excitation of device are 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 illustrate partial exploded view of the infusion device 100 during the installation of release mechanism, Fig. 8-Figure 10 is illustrated The exploded view and sectional view of infusion device 100 after the activation, and Figure 11 and Figure 12 illustrate infusion device 100 in release mechanism Exploded view after expansion and sectional view.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 shell 104, release mechanism 108, flexibility Needle cover 112, top shell 116, reservoir sub-component 120, dosage end indicator (EDI) 124 and activator appliance button 128 swash Device button 128 living includes patient interface surface 132.In addition, as shown in Fig. 2-Fig. 6, infusion device 100 further includes rotor or swashs Ring 136, pressing spring 140, arch metal plunger 144 and driving spring 148 living.

Flexible needle cover 112 is by protecting an at least needle 152 (being described in more detail below) and providing sterile barrier portion And provide the safety of patient and device.Needle cover 112 protects needle 152 during device manufacturing, protects patient before the use, and Any time before the removal provides sterile barrier portion.According to one embodiment, needle cover 112 attaches to needle discrimination via press-fit Pipe, at least a needle 152 are arranged in the needle manifold.In addition, according to one embodiment, the needle 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 160, reservoir arched sealing member 164, valve 168, at least a needle 152 and setting are between valve 168 and needle 152 and at them Between generate flow path at least one channel 172 (for example, with reference to Fig. 8).Reservoir 160 includes vault 176.In addition, storage Storage sub-component 120 includes that needle cover 112 can be removed selectively to cover an at least needle 152.According to one embodiment, storage Storage sub-component 120 further includes reservoir arm sealing element 180, to cover channel 172.Preferably, needle 152 include needle manifold and More micropins 152.

For example, as shown in Figure 5, the reservoir arched sealing member (flexible membrane) 164 of reservoir sub-component 120 is arranged in column Between plug 144 and vault 176.Reservoir contents (for example, medicinal material) for infusion device 100 are arranged to encircle between reservoir In space between shape sealing element 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 of on-expansible material or laminated material (such as metal coating or other similar substances).For example, can be A kind of possible flexible layer press mold used in reservoir arched sealing member 164 includes in the first polyethylene layer, such as this field Second chemosphere known to technical staff with provide the attachment mechanism for the third metal layer to being chosen based on barrier feature, And the 4th layer including polyester fiber and/or nylon.By with rigid element (for example, vault 176) in conjunction with using metal Plated film or metalized film improve the barrier properties of reservoir 160, to increase or improve the guarantor for 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) (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 further include COC and LLDPE and thermoplastic Property elastomer (TPE), medical grade acrylic acid, stainless steel and needle adhesive (for example, the cured adhesives of UV).With reservoir 160 Content keep this material for extending contact preferably to pass through ISO10-993 and other applicable biocompatibilities tests.

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

Other than meeting stability requirement, reservoir sub-component 120 can also be to successfully pass any number of leakage It tests (such as the sample of 30psi is kept into 20 minutes No leakages) and ensures to operate.As described in more detail below, it is derived from Other fillings, storage and the conveying benefit of the configuration of reservoir include the head space of adaptability and reduction.

In one embodiment, reservoir 160 empties before filling.By emptying reservoir 160 before filling simultaneously And in vault 176 only have slight recess portion, can by reservoir 160 excessive waste and head space be preferably minimized. In addition, the shape of reservoir can be configured to the type suitable for used excitation mechanism (for example, pressing spring 140 and plunger 144).In addition, being reduced in the reservoir 160 for being located at and filling using the flexible reservoir 160 being drained during filling Arbitrary air or bubble.In infusion device 100 being subjected to the variation of external pressure or temperature using flexible reservoir 160, (this can Lead to increased reservoir internal pressure) when be also particularly advantageous.In this case, flexible reservoir 160 and reservoir Content expansion and contraction together, to which prevent may leakage caused by expansion and contraction power.

The further feature of reservoir 160 include be allowed in filling the moment carry out the ability of particle inspection automatically 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 substance 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 clarity, low extract (low extractables), And the biocompatibility with the substance 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 obtains, and is stepped on by U.S.'s food and Drug Administration It is denoted as DMF No.16368.In this applications, reservoir 160 includes that minimum possibility hinders the feature checked (that is, being allowed in It is rotated during inspection).

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

Channel arm 172 must be sufficiently flexible to bear activating force.The position of channel arm 172 in comparison diagram 2 and Fig. 8, when It (is described in more below) when micropin 152 is driven in patient skin, channel arm 172 is (by reservoir arm sealing element in Fig. 2 180 coverings, for the sake of clarity, reservoir arm sealing element 180 is removed in fig. 8) flexible deformation.During the deformation, lead to Road arm 172 must be maintained between the integrality of the fluid path between valve 168 and needle manifold or micropin 152.In addition, being used for channel The material of arm 172 meets various biocompatibilities and storage is tested.For example, as shown in following table 1, when in infusion device It is tolerant when including insulin, the dominant touch material in reservoir 160 include linear low density polyethylene, cyclic olefine copolymer and Teflon, and also can include transparent clearly plastics.Residual stream between reservoir 160 and the micropin 152 of needle manifold Dominant touch material in dynamic path (channel 62) include COC and/or medical grade acrylic acid, LLDPE, TPE and stainless steel and Needle adhesive.

Table 1

More specifically, micropin 152 can be made of stainless steel, and needle manifold can be by polyethylene and/or medical grade propylene Acid is constituted.This material is preferably tested by ISO10-993 biocompatibilities when being contacted with the extension of the content of reservoir.

Reservoir 160 and channel are selectively allowed and limited to the valve 168 being arranged between reservoir 160 and channel 172 Fluid flowing between 172.Valve 168 preactivate position (for example, shown in Fig. 2, Fig. 3 and Fig. 6) and activated positon (for example, Shown in Fig. 8-Figure 10) between move.When in activated positon, valve allows the fluid stream between reservoir 160 and channel 172 It moves and thus allows to flow to the fluid of needle manifold and micropin 152.

When in use, valve 168 will be finally pushed into activated positon by the movement of activator appliance button 128, this is by valve 168 Movement between Fig. 5 and Figure 10 most preferably illustrates.As shown in Figure 10, the movement of valve 168 makes the enlarged distal tip portion row of valve 168 Into to allow drug out of reservoir 160 flow channel 172 and flow down through fluid path to reach needle manifold.

Above-described embodiment includes at least a needle 152 or micropin 152, but may include that several (such as two) illustrate Micropin 152.Every micropin 152 is preferably at least 31 dividers (gauge) or smaller such as 34 dividers, and being anchored at can It is arranged as in the patient's needle manifold being in fluid communication with reservoir 160.Micropin 152 is when infusion device 100 includes more than one Also can be able to include one with the combination of different length or divider or different length and divider, and along body length A or multiple ports, the port is preferably provided in the needle point of micropin 152 nearby or pinpoint inclined plane is (if any micropin 152 There are one tools) near.

According to one embodiment, the delivery rate of the reservoir contents of the divider control infusion device 100 of micropin 152. It is defeated when being carried out on the period longer with middle injector injection (needle guard or needle that need bigger) the associated period than usually When note, using multiple 34 dividers 152 come to convey reservoir contents be practical.In the disclosed embodiment, target can be used Be intradermal or subcutaneous space arbitrary micropin 152, but diagram embodiment include length between 1mm and 7mm (for example, 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 above-mentioned, micropin 152 is located in needle manifold.In needle manifold, every micropin 152 connects equipped at least one fluid Path or channel 172.Manifold can only have single path for one or more micropins 152, or can be arranged and will store Storage content is dividually routed to multiple fluid paths or the channel of every micropin 152.These paths or channel can be with Include for contents into crooked route, to influence Fluid pressure and delivery rate, and as flow limiter.Position In in needle manifold path or channel can depend on application and to width, depth and configuration setting range, wherein channel width It typically ranges between 0.015 inch and 0.04 inch, it is therefore preferable to 0.02 inch, and be configured to reduce dead in manifold Angle.

According to one embodiment, reservoir sub-component 120 has a pair of holes 184 and 188 to help reservoir sub-component 120 It is positioned about bottom shell 104.First column 192 of bottom shell 104 and the second column 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, it includes base that Fig. 4, Fig. 7 and Fig. 9, which illustrate bottom shell 104, 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, to guide the correspondence of plunger 144 multiple when plunger moves in shell 200 Leg 208 and foot 212.Leg 208 and foot 212 collectively form plunger protrusion 214.For example, as shown in Fig. 4, Fig. 7 and Fig. 9, recess is logical Road 204 extends only along cylindrical shell 200 from the part in the path of the top down of cylindrical shell 200.It is logical in recess Opening 216 is equipped with below road 204, the foot 212 of plunger 144 can extend to the outer of cylindrical shell 200 by opening 216 Side.Be open 216 substantially L-shaped, have 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 by plunger 144 (for example, such as Fig. 4-Fig. 6 Shown in), and the foot 212 of plunger 144 is substantially disposed in the horizontal component of opening 216.The power of pressing spring 140 makes plunger 144 foot 212 is biased against the top (for example, 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 around cylindrical shell 200 base portion preactivate position (for example, figure Illustrated in 2- Fig. 4) it is rotated between activated positon (for example, being illustrated in Fig. 8-Figure 10).When rotor 136 is rotated from preactivate position When to activated positon, at least one foot engagement pistons 144 for being engaged with the surface 220 (for example, shown in Fig. 4) of rotor 136 At least one of foot 212 and so that plunger 144 is rotated 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 moves up and foot 212 is guided by rising passway 204.

Pressing spring 140 is included in apply substantially homogeneous power to reservoir 160 in infusion device 100, by content Object is expelled from reservoir 160.Pressing spring 140 is used for storage energy, 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 Close the film (described below) for preventing pressing spring 140 from putting stress upon reservoir 160 during storage or arbitrary remaining dress It sets on component (other than bottom shell 104 and plunger 144).Plunger 144 is sufficiently rigid to resist spring tension and deformation, and And it should not fail under common load.

As above-mentioned, when rotor 136 is rotated from preactivate position to activated positon, the foot 212 of rotor 136 and plunger 144 At least one of engage, and make plunger 144 rotate so that foot 212 with opening 216 vertical portion and recess channel 204 Alignment.The pressing spring 140 of compression then moves up plunger 144, and exerts a force to the film of reservoir 160 thus On.Pressing spring 140 can be configured to preferably generate 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 the intradermal delivery of reservoir contents.In order to percutaneous Injection or infusion, the range 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 further includes hinge arms 224 and activation arms 228 (for example, being shown in FIG. 3).Swash The hinge arms 224 of device button 128 living include the cylindrical portion with opening.Activation arms 228 include protrusion 230 (for example, with reference to Fig. 3).According to one embodiment, protrusion 230 is including load-bearing surface 232 and is set as the cantilevered end phase with load-bearing surface 232 Adjacent locking surface 234.According to one embodiment, protrusion 230 and the major part of activation arms 228 form acute angle.

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

According to one embodiment, Fig. 3 and Fig. 6 illustrate position of the activator appliance button 128 relative to bottom shell 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 and (passes through planar side 236) and engaged with the first column 192.Hinge arms 224 (and thus activator appliance button 128) It is then able to rotate around the first column 192.When activation arms 228 are moved between the second column 196 and the first driving spring base portion 244 Space in when, raised at least one of 230 and activation arms 228 flexible deformation, until the load-bearing surface 232 of protrusion 230 Until holding surface 252 of the cantilevered end by the second column 196.The cantilevered end movement of the load-bearing surface 232 of protrusion 230 By the holding surface 252 (for example, with reference to Fig. 4) of the second column 196 and the locking surface 234 of protrusion 230 and holding surface 252 Engagement provide sense of hearing click sound and touch feedback that expression activator appliance button 128 is in preactivate position.

Referring back to Fig. 2-Fig. 4 and Fig. 7-Fig. 9, rotor 136 also comprises activation protruding portion 256 and driving spring is kept Device 260.When patient urges activator appliance button 128, the activation arms 228 of activator appliance button 128 connect with activation protruding portion 256 It closes, to make rotor 136 be rotated from preactivate position to activated positon.

When rotor 136 is in preactivate position, driving spring 148 is maintained at preactivate by driving spring retainer 260 In position.It has been observed that the opposite end of the first and second driving spring base portions 244 and 248 anchoring driving spring 148.It is driving At the approximately mid-point of spring 148, be equipped with the substantially U-shaped protruding portion as shown in such as Fig. 2 and Fig. 3, for rotor 136 Driving spring retainer 260 engages.Therefore, when rotor 136 is in preactivate position and driving spring 148 is protected with driving spring When holder 260 engages, driving spring 148 is maintained at tensional state.And when driving spring retainer 260 releases loose driving spring 148 (that is, when rotor is rotated from preactivate position to activated positon as shown in such as Fig. 8-Figure 10), driving spring 148 Drive micropin 152 with (hereafter more detailed and by the opening in release mechanism 108 by the opening 300 in bottom shell 104 Thin description) extend to the outside of infusion device 100.

As a result, as will be described in more detail below, swashing for infusion device 100 is realized with single multi-functional/step process Living and excitation includes urging activator appliance button 128 and rotor 136 due to the activation arms 228 in activator appliance button 128 by patient It is rotated caused by engagement between the activation protruding portion 256 of rotor 136.As described above, the rotation of rotor 136 makes plunger 144 rotate and release loose plunger 144 with the fluid being located in reservoir 160 that pressurizes.In addition, the rotation of rotor 136 is by driving spring 148 release pine from driving spring retainer 260, to drive micropin 152 to extend to the outside of infusion device 100.It is single more Function/step process further includes making valve 168 since activator button 128 engages and move valve 168 when activator button 128 is urged From preactivate position to the movement of activated positon, to start stream of the fluid via channel 172 between reservoir and micropin 152 It is dynamic.

As above-mentioned, patch-like infusion device 100 further includes release mechanism 108.Be not intended in order to prevent or unexpected needlestick injury, The intentional of anti-locking apparatus recycles and in order to shield exposed needle, is equipped with locking pin release mechanism 108.When by infusion device 100 automatically and immediately activate release mechanism 108 when being removed from patient skin surface.According to an implementation being described in more below Example, flexible adhesion pad 264 are attached to the bottom point of bottom shell 104 and the bottom point of release mechanism 108.Adhesive pad 264 and trouble Person's skin is in contact and keeps infusion device 100 in place on a skin surface during use.For example, as in Figure 11 and Figure 12 Shown, when removing infusion device 100 from skin surface, release mechanism 108 extends to the position of shielding micropin 152.When complete When full extension, release mechanism 108 locks unexpected injury or exposure in place and that prevent patient's needle 152.

In general, passive type security system is most desired.This makes device the case where surprisingly removing or patient forgets to be equipped with It can be from protection in the case of security step.It is supplied since a kind of typical use of this infusion device 100 is to provide usual night The human growth hormone answered, therefore the patient (such as children) that can desirably dress the device can actually dress 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 is fallen, then micropin 152 can be pierced into again in patient or caretaker's body.Solution is limitation activity during use Or including passive type security system.

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

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

When removing infusion device 100 from skin, flexible adhesion pad 264 (is attached to the bottom surface of bottom shell 104 With the bottom surface of release mechanism 108) release mechanism 108 and will be safe before adhesive pad 264 releases loose skin surface will be pulled out Mechanism 108 locks in place.In other words, adhesive pad is removed to required power from skin surface and is more than 108 institute of expansion release mechanism The power needed.According to one embodiment, for example, as shown in Figure 13, release mechanism 108 include be in contact with patient skin it is flat Surface portion 268.Flat surfaces 268 are in following positions：A part (shown in dotted line 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 by patient from skin, adhesive pad 264 will work will pacify Full mechanism 108 is unfolded from infusion device 100, otherwise should when removing infusion device 100 from patient to shield micropin 152 Micropin 152 will expose.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 as basic two parts, a bottom table for being located at bottom shell 104 In the major part in face, and one is located on the bottom surface of release mechanism 108.When infusion device 100 is removed, two patches are only It stands movement and release mechanism 108 can be rotated relative to bottom shell 104.According to another embodiment, two parts are formed as The flexible adhesion pad 264 of integral type, one of part are arranged in the major part of the bottom surface of bottom shell 104, and one Part is arranged on the bottom 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 shell 104 is made.As shown in Figure 14, release mechanism 108 exists including preceding shielding part 272, setting A pair of marginal portion 284 be inserted into protrusion 276, be separately positioned on release mechanism 108 at the rear part of release mechanism 108 it is upper A pair of of pivot protrusion 280 at rear end, the guide post upwardly extended from the bottom interior surface of the substantially flat of release mechanism 108 288 and the locking column 292 that is also upwardly extended from the bottom interior surface of release mechanism 108.Preceding shielding part 272 is in marginal portion Extend on 284 to make patient shield with micropin 152 when release mechanism 108 is unfolded.Guide post 288 includes the recess being located therein Protruding portion 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 It engages, to prevent release mechanism 108 to be unfolded before the activation of infusion device 100.

In addition, as above-mentioned, release mechanism 108 includes needle opening 156.Before release mechanism 108 is unfolded, needle opening 156 It is least partially overlapped to provide the space moved for micropin 152 with the opening 300 in bottom shell 104.Locking column 292 is distinguished It is set as adjacent with the forward edge of needle opening 156.Bottom shell 104 includes guide post opening 304 (for example, in Fig. 7 and Fig. 9 It is shown), be set as with the opposite side edge adjacent pair of bottom shell 104 be inserted into bump openings 308 (for example, being shown in Fig. 4 One of those) and a pair of seat 312 that pivots for being arranged in the opposite sides of bottom shell 104 (for example, Fig. 7 and figure Shown in 9).

Referring again to Figure 14, it includes coupling part 316 and extension 320 to be inserted into protrusion 276 respectively.Implemented according to one Example, coupling part 316 is from the bottom interior surface of release mechanism 108 towards the rear of infusion device 100 with about release mechanism 108 Bottom interior surface extend at non-perpendicular angle.Extension 320 is respectively from extension 320 towards the phase of release mechanism 108 Outside is answered essentially perpendicularly to extend.In order to which release mechanism 108 to be assembled into bottom shell 104, release mechanism 108 is remained About bottom shell 104 at about 45 ° of angle, and protrusion 276 will be inserted into it is inserted through and be inserted into bump openings 308.Then By the rotation of release mechanism 108 a to 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 bottom surface of bottom shell 104 and be in contact with the bottom surface.

Referring again to Fig. 7 and Fig. 9, although these views illustrate the rotor 136 in activated positon, Fig. 7 and Release mechanism 108 is assembled into the stage in bottom shell 104 convenient for diagram by the resolution characteristic of Fig. 9.It is to be understood, however, that It is release mechanism 108 to be assembled into bottom shell before activation.As shown in Figure 4, upward in release mechanism 108 After rotation, release mechanism 108 is moved backward relative to bottom shell 104 so that pivot protrusion 280, which is crossed, pivots seat 312 Corresponding leading edge and be arranged in the top for pivoting seat 312, locking column 292 is set as and the opening of bottom shell 104 300 Lateral edges it is adjacent, and rotor 136 safety keep protruding portion 296 engaged with guide post 288.

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

When release mechanism 108 is unfolded and when being rotated down relative to bottom shell 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 flexible deformation toward each other of locking column 192.When release mechanism 108 is complete When full expansion, protrusion 280, which becomes resting against, to be pivoted in seat 312.In addition, the top edge of wedge-like portion 328 is by opening 300 Feather edge, and locking column 292 skips back to its basic undeformed state, to provide sense of hearing click sound and touch feedback to express Release mechanism 108 is fully expanded and thus micropin 152 is capped.It is back to Figure 11 and Figure 12, once release mechanism 108 is complete Full expansion and locking column 292 have skipped back to its basic undeformed state, the top edge of wedge-like portion 328 just with 300 phases that are open Adjacent ground is engaged with the bottom surface of bottom shell 104, to prevent release mechanism 108 from being rotated up relative to bottom shell 104, And prevent micropin 152 from exposing.In addition, as above-mentioned, preceding shielding part 272 makes patient be shielded 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, there is no other power to be applied on skin during injection, And micropin 152 is retained securely in infusion device 100 after usage.

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

EDI124 further includes the spring arm 344 being bent upwards from 332 top of main body.According to one embodiment, spring Arm 344 is pushed against the bottom side of reservoir sub-component 120, to make EDI124 towards 104 elastic biasing of bottom shell, to ensure Such as EDI124 will not move freely through out infusion device 100 during the transport and disposition of infusion device 100.According to a reality Example is applied, spring arm 344 is pushed against the bottom side of vault 176.

It is back to Fig. 4, main body 332 is arranged in the channels EDI 348 and generally vertically moves in the channel.According to one A embodiment, the channels EDI are set as adjacent with one in the recess channel 204 of the leg 208 of guiding plunger 144 and foot 212.The One arm 336 extends across the top of the recess channel 204.

Figure 15 A, vertical extrusion or beacon 352 is back to upwardly extend from the end of the second arm 340.It will storage when When storage content exports, beacon 352 extends through 356 (for example, with reference to Figure 15 C) of opening of the EDI in top shell 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 and in cylindrical shell 200 to When upper traveling, one in the foot 212 of plunger 144 is in contact with the first arm 336 of EDI124.The phase is conveyed in reservoir contents Between, EDI124 is lifted by foot 212 upwards, to overcome the biasing of spring arm 344, and beacon 352 is caused gradually to extend through Cross EDI openings 356.Referring back to Figure 10, when drug is just discharged from reservoir 160 after activation, beacon 352 is filled from infusion 100 are set partly to extend.Once the conveying completion of reservoir contents and plunger has been carried out its complete stroke, vertical to squeeze Part 352 is just fully extended, as shown in Figure 15 D.EDI124 uses the linear movement of plunger 144 to generate EDI124 as a result, Linear movement, the linear movement of the EDI124 can be in the outside of infusion device 100 as it can be seen that express reservoir contents Conveying.

Figure 16 A and 16B illustrate another dosage end indicator (EDI) 360 and its behaviour in infusion device 100 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, base portion 364 is visible on the outside of infusion device 100 shows that the conveying of drug 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 includes main body 376, the first arm 380 extended from main body 376 and the first spring arm 384 also extended from main body 376 With second spring arm 388.In addition, 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, the remainder of at least part and beacon 392 of base portion 396 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 object is substantially finished.

As shown in figure 17 a, EDI372 further includes a pair of of the arm of stability 412 and 416 extended from main body 376.The arm of stability 412 Stablize EDI372 in EDI372 moving process with 416.Figure 18 illustrates the EDI372 being arranged in infusion device.In Figure 18 Shown, cylindrical shell 200 includes the channel 420 for the main body 376 for being removably received by EDI372.The arm of stability 412 and 416 contacts The outside of cylindrical shell 200 in EDI372 moving process to stablize EDI372.

After the activation, when plunger 144 is advanced in cylindrical shell 200, the foot 212 of plunger 144 is contacted and is lifted The main body 376 of EDI372, therefore by based on the conversion of motion of plunger 144 376 movement and the thus fortune of beacon 392 It is dynamic.

First spring arm 384 and second spring arm 388 all have be set to its respectively the spring arm column 404 of end, 408.According to one embodiment, spring arm column 404 and 408 contacts the bottom side of reservoir sub-component 120, to make EDI372 together with Spring arm 384 and 388 is elastically inwards biased relative to top shell 116, to ensure before dosage terminates (such as transporting During disposition infusion device 100) EDI372 is not extend to except infusion device 100.According to one embodiment, spring arm column 404 and 408 are pushed against the bottom side of vault 176.

When plunger 144 arrives at the terminal of its traveling stroke, power that pressing spring 140 acts on plunger 144 overcomes the The biasing of one spring arm 384 and second spring arm 388, to thus cause signal column 392 extends to except infusion device 100 and Show that the conveying of drug 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 column 428 for having helical form face 432.EDI424 further include the arm 436 extended from the end of column 428 and Vertical extrusion or beacon 440, the vertical extrusion or beacon 440 are extended across from the end of arm 436 outside top EDI in shell 116 is open 444 (see Figure 20 A) with can be from 100 outside of infusion device.According to one embodiment, EDI is opened Mouth 444 is arcuate slot.Column 428 also has the base portion 448 for EDI424 to be rotationally attached to bottom shell 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, the helical form face 432 of EDI424 carries in the entire motion process of plunger Against the edge of plunger 144.Therefore, when plunger 144 travels 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 motion process of plunger Interaction between middle helical form face 432 and the edge of plunger 144 is led to less than one complete rotation circle of the rotation of column 428 Number.In other words, the screw pitch in helical form face 432 is led to that column 428 rotates less than one complete rotation in 144 motion process of plunger The number of turns.

When EDI424 rotates, the correspondingly rotation in EDI openings 444 of beacon 440.And when beacon 440 arrives at When the end of EDI openings 444, as illustrated in figure 2 ob, the conveying of EDI424 instruction drugs is substantially finished.

Similar to Figure 19 A and 19B, Figure 21 A and 21B illustrate another dosage end indicator (EDI) 452 and its behaviour Make.As shown in figure 21 a, EDI452 includes the column 456 for having helical form face 460.In addition, column 428 has for by EDI452 It is rotationally attached to the base portion 462 of bottom shell 104.EDI452 further includes signal indicator 464 on top of this, signal Indicator 464 can be open 468 (see Figure 22 A) from 100 outside of infusion device by the EDI in top shell 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, the helical form face 432 of EDI424 carries and supports in the entire motion process of plunger By the edge of plunger 144.Therefore, when plunger 144 travels 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 screw pitch.Therefore, EDI452 is rotatably more in plunger 144 and EDI424 stroke procedures.According to one embodiment, Interaction in 144 motion process of plunger between helical form face 460 and the edge of plunger 144 is led to the rotation of column 456 at least One complete rotating cycle.In other words, the screw pitch in helical form face 460 is led to rotates extremely in 144 motion process center pillar 456 of plunger A few complete rotating cycle.According to one embodiment, EDI452 rotates complete more than one in the stroke procedure of plunger 144 Whole rotating cycle.

According to one embodiment, signal indicator 464 is such as arrow.Correspondingly, with EDI be open 468 adjacent tops There are at least one labels 472 on the exterior section of portion's shell 116.When EDI452 is open due to the stroke of plunger 144 in EDI In 468 when rotation, signal indicator 464 can be from 100 outside of infusion device as it can be seen that thus referring to relative to the rotation of label 472 Show the process of drug conveying.

According to one embodiment, the screw pitch in helical form face 460 be defined as being led to column 456 plunger 144 stroke procedure Middle rotation just less than two complete rotating cycles.Therefore, as shown in Figure 22 B, in just less than 2 complete rotations of advancing It turn-takes after number, the conveying of EDI452 instruction drugs is substantially finished.

As shown in Figure 23 A-23C, it may be used and be open adjacent various labels with the EDI in top shell 116 to refer to Show the process of drug conveying.For example, Figure 23 A illustrate label 476, shown label 476 includes the scale for having scale.It is this It can be used together with EDI424 with the label 476 of arch EDI opening pairings.However usually will be understood that, it is various Label can also use together with variously-shaped EDI openings and various EDI embodiments.

Figure 23 B illustrate label 480, and the label 480 includes the symbol for the expanded state for indicating reservoir 160.For example, One symbol instruction reservoir 160 is substantially saturated with, and intermediate symbols instruction reservoir 160 is substantially saturated with half and therefore medicine The conveying of object is substantially finished half, and third symbol instruction reservoir 160 is substantially empty and therefore drug defeated It send and is substantially finished.

Figure 23 C illustrate label 484, depend on the direction of rotation of corresponding EDI, and the label 484 includes indicating to store The score symbol of the expanded state of storage 160 or the score of the drug conveying of completion.For example, if there is arrow signal indicator The EDI that rotates clockwise used together with label 484, then the movement of the EDI will indicate reservoir 160 expanded state.On the contrary Ground, if the rotation EDI counterclockwise with arrow signal indicator is used together with label 484, the movement of the EDI will indicate The score for the drug conveying 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 conveying is basic Upper completion.Because the top (such as the window being placed in one) of reservoir is transparent, color change is visible.

According to one embodiment, EDI488 is set in reservoir 160, such as in the interior surface of transparent vault 176. In the terminal point 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 element 164 is transferred to Pressure Sensitive Tape 488, 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 set in the ontology of infusion device 100 with can be from can from 100 outside of infusion device See.In addition, EDI488 is arranged so that the foot 212 of plunger 144 is due to adding when plunger 144 arrives at the terminal of its traveling stroke The power of pressing spring 140 and contact Pressure Sensitive Tape 488, and the face of Pressure Sensitive Tape 488 is led to against the pressure of the foot of Pressure Sensitive Tape 488 212 Color change.Figure 24 B and 25B, which are illustrated, to be contacted Pressure Sensitive Tape 488 in foot 212 and is led to color change to indicate that drug conveying is completed 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 packet of the chamber 496 and 500 at least two separation.When plunger 144 arrives at the terminal of its traveling stroke When, the pressure of plunger 144 is given to dyestuff packet 492 (due to the power of pressing spring 140), to make 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 conveying is substantially finished.

According to one embodiment, chamber 496 is with yellow dye and chamber 500 is with blue dyestuff.Once separator 504 is broken It splits, blue dyestuff and yellow dye mix and formed green dye, to indicate that drug conveying is substantially finished.

According to one embodiment, EDI492 is set in reservoir 160, such as on the inner surface of transparent vault 176. The terminal point 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 element 164 is transferred to dyestuff packet 492, 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 set in the ontology of infusion device 100 with can be from can from 100 outside of infusion device See.In addition, EDI492 is arranged so that the foot 212 of plunger 144 is due to adding when plunger 144 arrives at the terminal of its traveling stroke The power of pressing spring 140 and contact dyestuff packet 492, and against the pressure of the foot of dyestuff packet 492 212 make separator 504 rupture simultaneously And it is led to the color change of dyestuff packet.Figure 26 B and 27B illustrate foot 212 contact dyestuff packet 492 and be led to color change to Indicate the infusion device 100 that drug conveying 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 the close of the reservoir 708 of filling so that the combination of substance or substance can be injected into reservoir by patient before activation It is interior.Optionally, pharmaceutical production person or pharmacists can use injection port 704 to use the group of substance or substance 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 Button 128) design, wherein infusion device 100 can position and be attached to skin surface, and by urging activator appliance button 128 And it is energized and/or activates.More specifically, in first step, patient's moving-out device, removal from aseptic packaging (not shown) is viscous Close the lid (not shown) of pad 264.Patient also removes needle cover 112.When removing infusion device 100 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 the medicament of inspection loss or the component, Expiration Date, atomization or the color offset that damage, etc..

It is that infusion device 100 is positioned and is applied on the skin surface of patient in next step.As patche, patient Infusion device 100 is urged on the skin securely.The side of adhesive pad 264 is attached to the bottom surface and peace of bottom shell 104 The bottom surface of full mechanism 108, and infusion device 100 is fixed to the skin of patient by the opposite side of adhesive pad 264.These (bottoms Shell 104 and release mechanism 108) bottom surface can be flat, curve or shape in any suitable manner, and And adhesive pad 264 is fixed on these bottom 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 above-mentioned, before the use, patient is peeled off Adhesive cover, to make the exposure of adhesive pad 264 for being arranged against skin.

After removing adhesive cover, patient can arrange infusion device 100 against skin, and urge to ensure suitably Attachment.As above-mentioned, once appropriate positioning, just activates the device by urging activator appliance button 128.The activation step releases pine Plunger 144 and pressing spring 140, to enable plunger 144 to be urged against the flexible membrane of reservoir 160, (reservoir arch is close Sealing 164), to pressurizing reservoir.The activation step is additionally operable to keep driving spring 148 from the driving spring of rotor 136 Device 260 releases pine, to drive micropin 152 (to be opened by the needle of opening 300 and release mechanism 108 in bottom shell 104 with extension 156) mouth rests on patient's body to the outside of infusion device 100 and by micropin 152.In addition, activation step makes valve 168 beat It opens, to establish between reservoir 160 and micropin 152 via the fluid communication road of channel 172 (for example, with reference to Fig. 8-Figure 10) Diameter.Significant benefit is derived from the ability of each realized with single button operation in these actions.In addition, another significant Benefit includes using the continuous fluid communication path being entirely included in reservoir sub-component 120.

Once being activated, patient is typically by infusion device within a period of time (such as ten minutes to 72 hours) 100 retain complete conveying of the in place or object wearing device for reservoir contents.Drug conveying is basically completed by EDI (examples Such as, EDI124) instruction.Patient then removes and drop device is without with destruction following skin or tissue.When deliberately or When unexpected removal, one or more security features expansion are to shield exposed micropin 152.More specifically, when infusion device 100 by When patient removes from skin, adhesive pad 264 makes release mechanism 108 be unfolded from infusion device 100, to shield micropin 152, Otherwise when removing infusion device 100 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 unfolded, to prevent release mechanism before use to be unfolded. After use, patient can check again for device to ensure that entire 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 implementing many kinds of substance, including drug and medicine to patient and especially human patients With agent.As used herein, medicinal agent include can be carried through body film and surface and in particular skin have bioactivity Substance.The example enumerated in further detail below includes antibiotic, antivirotic, analgestic, anesthetic, fenisorex, Antiarthritic Medicine, antidepressants, antihistamine, antiphlogistic, antineoplastic, vaccine (including DNA vaccination) etc..It can be intradermal or subcutaneous to patient Other substances of conveying include human growth hormone, insulin, albumen, polypeptide and its fragment.Albumen and polypeptide can be nature What occurring, synthesis or recombination generated.In addition, the device can use in cell therapy, such as in the intradermal of dendritic cells During infusion.Other substances that can be conveyed according to the method for the present invention can from by prevention, diagnosis, mitigation, treat or control It is chosen in the group of the compositions such as the drug, the vaccine that are more used in disease, wherein drug includes：α -1 antitrypsins, anti-angiogenic life It is patent medicine, antisense, butorphanol, calcitonin and the like, Ceredase, II inhibitor of COX-, Dermatological Agents, dihydroergotamine, more Bar amine receptor agonist and antagonist, enkephalins and other opioid peptides, epidermal growth factor, hematopoietin and similar Object, follicular stimulating hormone, G-CSF, glucagon, GM-CSF, Granisetron, growth hormone and the like (including growth hormone Releasing hormone), growth hormone receptor antagonist, hirudin and hirudin analog (such as hirudin), IgE inhibitor, pancreas islet Element, pancreotropic hormone and the like, swash lutern, human luteinizing hormone at insulin-like growth factor, interferon, interleukins Releasing hormone and the like, low molecular weight heparin, M-CSF, metoclopramide, Midazolam, monoclonal antibody, narcotic analgeiscs, Nicotine, non-steroidal anti-inflammatory drug, oligosaccharide, Ondansetron, parathyroid hormone and the like, parathyroid hormone receptor are short of money Anti-agent, prostaglandin antagonists, prostaglandin, recombinant soluble receptor, hyoscine, hydroxytryptamine agonist and antagonist, sulphur Acyl pyrimidine benzene, Terbutaline, thrombolytics, histoplasmosis activator, TNF and TNF- antagonists；Vaccine, with or without load Body/adjuvant, including with following relevant preventative and therapeutic antigens (include but not limited to protein subunit, polypeptide and polysaccharide, more Sugared conjugate, toxoid, the vaccine based on gene, attenuated live vaccine, re-match strain vaccine, deactivation vaccine, full cell, virus and Bacteria carrier)：Addicted, arthritis, cholera, cocaine addiction, diphtheria, lockjaw, HIB, Lyme disease, meningitis, measles, the parotid gland Inflammation, rubella, varicella, yellow fever, respiratory syncytial virus, tick-borne encephalitis B, pneumococcus, streptococcus, typhoid fever, stream Sense, hepatitis (including A types, Type B, c-type and E types hepatitis), tympanitis, rabies, polioencephalitis, HIV, parainfluenza virus, colyliform Virus, Epstein-Barr virus, CMV, Chlamydia, typeable haemophilus, moraxelle catarrhalis, human papilloma virus, pulmonary tuberculosis (including BCG), gonorrhoea, asthma, arteriosclerosis, malaria, Escherichia coli, senile dementia, helicobacter pylori, salmonella, sugar Disease, cancer, herpes simplex virus, human papilloma and other similar substances are urinated, other objects of all primary treatments are included Matter, such as common cold drug, drug-breaking medicine, antiallergic, antiemetic, antiadipositas drug, anti-osteoporotic, anti-infectious agent, analgesia Medicine, arcotic, fenisorex, anti-arthritic, antiasthmatic, anticonvulsive drug, antidepressants, antidiabetic drug, antithistamine, anti-inflammatory Medicine, antimigraine, anti-motion sickness medicine, antiemetic, antineoplastic, anti-Parkinson syndrome medicine, antipruritic, antipsychotic, solution The medicine of a warm nature, anticholinergic agent, benzodiazepine receptors antagonist, vasodilator (including general blood vessel, coronary artery, external perihaemal canal and The cerebrovascular), osteo stimulative agent, central nervous system stimulant, hormone, hypnotic, immunosuppressor, muscle relaxant, parasympathetic Nerve block medicine, parasympathomimetics, prostaglandin, albumen, peptide, polypeptide and other macromoleculars, excitant, sedative, property Hypofunction and sedative and Main Diagnosis are for example such as in the United States Patent (USP) of entitled " methods of intradermally injecting substances " The full content of No.6, the tuberculin described in 569,143 and other allergy medicaments, the patent is defined by way of reference It is incorporated herein.

The vaccine formulation for capableing of system and a method according to the invention conveying can be from by that can eliminate to human body cause of disease It is chosen in the group that the antigen or antigenic component of immune response are constituted, it is (such as broken that the antigen or antigenic component are derived from HIV-1 Wind antitoxin, nef, gp120 or gp160), nerpes vinrus hominis (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 Viral (including active attenuated virus), Epstein-Barr virus (such as gp350 or derivatives thereof), varicellazoster virus (VZV, such as GpI, II and IE63) or from hepatitis virus (such as hepatitis B virus (such as HbsAg or derivatives thereof), Hepatitis A virus (HAV), hepatitis C virus and E Hepatitis virus)；Or it is derived from other viral pathogens such as hepatitis virus Paramyxovirus：Respiratory Syncytial Virus(RSV) (RSV, such as F and G-protein or derivatives thereof), parainfluenza virus, measles virus, the parotid gland Scorching virus, human papilloma virus (HPV, such as HPV6, HPV11, HPV16, HPV18), flavivirus (for example, yellow fever virus, Dengue fever virus, tick-brone encephalitis virus, japanese encephalitis virus) or influenza virus (full activity or inactivation of viruses, cracking influenza virus (being grown in egg cell or mdck cell) or full influenza virus particles or its purifying or recombinant protein (such as HA, NP, NA or M albumen or combinations thereof))；Or it is derived from bacterial pathogen, such as neisseria, including NEISSERIA GONORRHOEAE and meningitis Neisser Bacterium (such as capsular polysaccharide and its conjugate, transferrin binding protein, newborn iron-binding protein, PiLC, bacterial cell surface are matched Base)；Micrococcus scarlatinae (such as M albumen or its segment, C5A protease, lipoteichoicacid), Streptococcusagalactiae, streptococcus mutans； Haemophilus ducreyi；Moraxella, including catarrh Morakot this Salmonella, also referred to as branhamella catarrhalis (for example, adhesins and invasion of high molecular weight and low molecular weight)；Bordetella, including bacillus pertussis (such as pertactin, pertussis toxin or derivatives thereof, filamentous hemagglutinin, adenyl cyclase, pili), pair hundred Day cough Bordetella and bordetella bronchiseptica；Mycobacterium, including mycobacterium tuberculosis (such as ESAT6, Antigen 85A, 85B or 85C), Mycobacterium bovis, Mycobacterium leprae, shame dirt paratuberculosis mycobacteria, mycobacterium paratuberculosis, 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 Such as congratulate toxin toxoid or derivatives thereof)；Vibrio, including comma bacillus (such as cholera toxin or derivatives thereof)；Shiga Bacillus, including Shigella sonnei, shigella dysenteriae, Shigella flexneri；Yersinia's genus, including yersinia enterocolitica (such as firelight or sunlight albumen), yersinia pestis, artificial tuberculosis yersinia genus；Campylobacter, including campylobacter jejuni (such as it is toxin, thin Bacterium cell surface ligand and invasion) and campylobacter coli；Salmonella category, including Salmonella typhi, paratyphoid A are husky Door bacterium, Salmonella choleraesuis, Salmonella enteritidis；Listeria, including Listeria monocytogenes；Helicobacter, Including helicobacter pylori (such as urase, catalase, cavitating toxin)；Pseudomonas, including Pseudomonas aeruginosa；Grape ball Pseudomonas, including staphylococcus aureus, staphylococcus epidermis；Enterococcus spp, including enterococcus faecalis, enterococcus faecium；Fusobacterium, packet Include clostridium tetani (such as tetanus toxin and its derivative), clostridium botulinum (such as botulin toxin and its derivative), Clostridium difficile (for example, clostridial toxins A or B and its derivative)；Bacillus, including Bacillus anthracis (such as botulinum toxin and its derivative)；Corynebacterium, including corynebacterium diphtheriae (such as diphtheria toxin and its derivative)；Bao Rou Family name's Spirochaeta, including Bai Shi Borrelias (such as OspA, OspC, DbpA, DbpB), Borrelia garinii (such as OspA, OspC, DbpA, DbpB), A Fuxini Borellias (such as OspA, OspC, DbpA, DbpB), Anderson Borellia (such as OspA, OspC, DbpA, DbpB), borrelia hermsii；Ehrlichia, including Ehrlichia equi and human granular leukocyte The medicament of property Paul Ehrlich body disease；Rickettsiae, including rickettsia rickettsii；Chlamydiaceae, including chlamydia trachomatis (such as MOMP, heparin-binding protein), chlamydia pneumoniae (such as MOMP, heparin-binding protein), chlamydia psittaci；Leptospira Belong to, including leptospria interrogans；Close rotation body category, including Spirochaeta pallida (for example, rare outer membrane protein), the close spiral shell of tooth dirt Revolve body, treponema hyodysenteriae；Or it is derived 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；Trypanosomonas, including schizotrypanum cruzi；Giardia, including Giardia lamblia；Leishmania, including it is large Big Leishmania；Pneumocystis, including pneumocystis pneumoniae；Trichomonas, including trichomonas vaginalis；Blood fluke, including Mans Blood fluke；Or it is derived from saccharomycete, such as Mycotoruloides, including Candida albicans；Cryptococcus, including cryptococcus；As It is announced described in No.WO02/083214, in the whole of this application in the PCT Patent Application of entitled " vaccine delivery system " Appearance is incorporated herein by way of reference.

These further include be used for other phthisical preferred specific antigens, such as Tb Ral2, Tb H9, Tb Ra35, Tb38-1, Erd 14, DPV, MT1, MSL, mTTC2 and hTCC1.Further include fusion protein and its change for phthisical albumen Kind, wherein phthisical at least two, preferred three peptide fusions are the albumen of bigger.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.The most preferred antigen for Chlamydia includes such as high molecular weight egg (HWMP), ORF3 and hypothesis memebrane protein (Pmps) in vain.Preferred bacterial vaccine includes the antigen from streptococcus, including Streptococcus pneumonia (such as capsular polysaccharide antigen and its conjugate, PsaA, PspA, streptolysin, choline binding protein) and Proteantigen pneumolysin (Biochem Biophys Acta, 1989,67,1007；Rubins et al., Microbial Pathogeneisi, 25,337-342 (biochemistry and biophysics document, 1989,67,1007；Lu Bin etc., Microorganism pathogenesis, page 25,337-342)) and its mutation detoxified derivaties thereof.Other preferred bacterial vaccines include being originated from It is thermophilic in the antigen of hemophilus, including Type B haemophilus influenzae (" Hib ", such as PRP and its conjugate), typeable influenza Blood bacillus (such as OMP26, high molecular weight bacterial cell surface adhesins, P5, P6, D albumen and L lipoprotein), And fimbrin and fimbrin derivative peptide or its multiple copy mutation or fusion protein.HbsAg spreads out Biology is well known in the art, and includes PreS1, PreS2S antigen etc..In a preferred aspect, of the invention Vaccine formulation includes HIV-1 antigens, gp120, especially when being expressed in Chinese hamster ovary celI.In a further embodiment, of the invention Vaccine formulation include gD2t as defined above.

Other than conveying substance listed above, infusion device 100 also can be used in extracting substance, Huo Zhejian from patient Control the level of substance in patients.The example for the substance that can be monitored or extract includes blood, interstitial fluid or slurry.It is taken out The substance taken can then be analyzed for analyte, glucose, drug 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, which are meant, is included in appended claims and its equivalent range.

Claims (5)

1. a kind of medicament delivery device, including：

Ontology, the ontology have shell and are arranged in the ontology for accommodating the reservoir of drug, the shell packet Recess channel and the opening below the recess channel are included, the opening includes the level at the base portion of the shell Part and the vertical portion being substantially aligned with the recess channel；

Injection needle, the injection needle are used to be pierced into the skin of patient, and the injection needle is connected to the reservoir fluid；

Presser unit；

Plunger, the plunger have foot and can under the action of the power of the presser unit in the ontology move with In the drug is discharged from the reservoir；And

Pointer device, the pointer device is visible on the outside of described device to be substantially finished for instruction drug conveying,

Wherein, the advance terminal of scheduled distance to its traveling stroke of the plunger triggers the pointer device, to change The color of the visible pointer device on the outside of described device；

Wherein, the plunger is advanced in the case where not making the pointer device move reaches at least one of the preset distance Point；

Wherein, when the medicament delivery device is in pre-activated state, the power of the presser unit keeps the foot of the plunger inclined Set the top of the horizontal component against the opening；

Wherein, when the medicament delivery device is active, the vertical portion of the foot of the plunger and the opening and Recess channel alignment, and the presser unit makes that the plunger moves up and the foot is drawn by the recess channel It leads；And

In the terminal of the traveling stroke of the plunger, the foot contacts the pointer device to trigger the pointer device, To change the color of the visible pointer device on the outside of described device.

2. the apparatus according to claim 1, wherein the pointer device includes Pressure Sensitive Tape；

Wherein, when the plunger arrives at the terminal of its traveling stroke, the pressure against the foot of the Pressure Sensitive Tape is led to institute The color change of Pressure Sensitive Tape is stated to be substantially finished for instruction drug conveying.

3. the apparatus according to claim 1, wherein the presser unit includes pressing spring.

4. a kind of medicament delivery device, including：

Ontology, the ontology have shell and are arranged in the ontology for accommodating the reservoir of drug, the shell packet Recess channel and the opening below the recess channel are included, the opening includes the level at the base portion of the shell Part and the vertical portion being substantially aligned with the recess channel；

Injection needle, the injection needle are used to be pierced into the skin of patient, and the injection needle is connected to the reservoir fluid；

Presser unit and plunger with foot, the plunger can be under the action of the power of the presser unit in the ontology Movement is for the contact reservoir；And

Pointer device, the pointer device is visible on the outside of described device to be substantially finished for instruction drug conveying, Wherein, the motion-activated pointer device of the plunger, and wherein, the pointer device is by the movement of the plunger It is converted into the movement of the visible pointer device on the outside of described device；

Wherein, the pointer device includes Pressure Sensitive Tape；

Wherein, when the medicament delivery device is in pre-activated state, the power of the presser unit keeps the foot of the plunger inclined Set the top of the horizontal component against the opening；

Wherein, when the medicament delivery device is active, the vertical portion of the foot of the plunger and the opening and Recess channel alignment, and the presser unit makes that the plunger moves up and the foot is drawn by the recess channel It leads；And

Wherein, when the plunger arrives at the terminal of its traveling stroke, the foot due to the power of the presser unit effect and Contact the Pressure Sensitive Tape, and the pressure of the foot against the Pressure Sensitive Tape be led to the color change of the Pressure Sensitive Tape for Instruction drug conveying is substantially finished.

5. device according to claim 4, wherein the presser unit includes pressing spring.