JP5058163B2 - Small pump that discharges medicine - Google Patents

Description

  [1] The present invention relates to a miniature infusion device or pump for dispensing a drug, and more particularly a reservoir having a shape memory alloy that is either superelastic or superdeformable It relates to a pump that uses

  [2] Metered drug delivery pumps typically utilize a metal bellows reservoir with a two-phase propellant to maintain the drug at a constant pressure of about 24 psi (about 36 psi). Yes. The drug flows out of the reservoir through a flow restrictor, such as a glass capillary calibrated to produce the desired flow rate. Fixed rate pumps are typically 80 cc to 100 cc in size. The reservoir utilizes a metal bellows made of a suitable material, such as titanium.

  However, such metal bellows are typically not very elastic and the reservoir must be of a relatively large size to accept accordion-like leaves. Such a construction hinders the design of a small pump and is expensive. The present invention addresses the problems associated with prior art pumps and can be utilized with either metered or variable volume, small size pumps that dispense medication.

  [3] In one embodiment, the present invention is an injection device used when discharging a medicine. The infusion device includes a housing having a chamber. The housing has an outlet. The diaphragm is operably connected to the pump housing, the diaphragm divides the chamber into a drug storage sub-chamber and a propellant sub-chamber, and the diaphragm is configured to extend on the centerline for greater volumetric efficiency. ing. The propellant subchamber is configured to receive a suitable propellant. The medication subchamber is configured to receive a suitable medication, and the medication reservoir has an outlet in fluid communication with the outlet of the housing.

  [4] In another embodiment, the present invention is an injection device used when a drug is discharged. The infusion device includes a housing having a chamber, the housing having an outlet. A diaphragm is operatively connected to the housing, the diaphragm dividing the chamber into a drug storage sub-chamber and a propellant sub-chamber, the diaphragm being made of a shape memory alloy material. The propellant chamber is configured to receive a suitable propellant, and the drug storage subchamber is configured to receive a suitable drug, and the drug storage subchamber has an outlet in fluid communication with the outlet of the housing. Have.

  [5] In another embodiment, the present invention is an infusion device used when discharging a medicine. The infusion device includes a housing having a chamber, the housing having an outlet. A diaphragm is operably connected with the housing, and the diaphragm divides the chamber into a drug storage sub-chamber and a propellant sub-chamber. The diaphragm is made of a shape memory alloy. The propellant subchamber is configured to receive a suitable propellant. The drug storage subchamber is configured to receive a suitable drug, and the drug storage subchamber has an outlet in fluid communication with the outlet of the housing. The flow restrictor has a first end in fluid communication with the outlet of the drug storage subchamber and a second end in fluid communication with the outlet of the housing. The flow restrictor is a micromachined flow restrictor, and the flow restrictor includes a first glass member having a planar top surface. The second glass member has a planar bottom surface, and the bottom surface of the second glass member is disposed on the top surface of the first glass member to form a chip assembly. A passage is machined on one of the top and bottom surfaces. The tip assembly has an inlet in fluid communication with the drug storage subchamber and an outlet in fluid communication with the outlet of the housing.

  [37] Referring to the drawings in which like parts are indicated by like reference numerals throughout the several views, a miniature pump for dispensing a drug as a whole is disclosed at 100. Although the pump 100 and the pumps of other embodiments described below can be described as implantable, it is understood that the pump can also be used as a non-implantable pump, such as a patch pump. Is done. 1a-1c, 2 and 3, the pump 100 includes a suitable housing 101 having a top half 101a and a bottom half 101b. The inner wall 102 is operatively connected to the housing and divides the interior of the housing 101 into an upper cavity 103 and a lower cavity 104.

  A dome-shaped diaphragm 105 is operatively connected to the housing 101 and the inner wall 102 and divides the lower cavity 104 into a drug storage subchamber 106 and a propellant subchamber 107. The propellant subchamber 107 can be filled with any suitable propellant, such as a two-phase propellant, as is well known in the art. The diaphragm 105 is made of a shape memory alloy such as NITINOL, which is a superelastic or superdeformable Ni-Ti alloy. Superelastic metallic materials allow a thin film to be displaced in multiple cycles while not breaking when encountering large strains. The superelastic metal material is superelastic so that it can undergo large elastic deformations or strains compared to typical metals. The thin circular diaphragm 105 has a dome shape that allows the membrane to move as the drug storage sub-chamber 106 changes from full to empty. The main bending stress formed by the diaphragm 105 is small and does not cause a significant pressure change to the drug in the drug storage subchamber 106.

  The diaphragm 105 can be made of a Ni-Ti alloy, i.e., a superelastic type material such as NITINOL. The specific composition of Nitinol can vary depending on the characteristics required, but Nitinol is about 55% Ni and 45% Ti, or, from another perspective, Ni and Ti are Each is about 50 atomic ratio. Useful results are obtained if this material is used in either its austenite or martensite phase. The nitinol material can be designed to resist the large strain generated by bending of the diaphragm 105 while the drug reservoir changes from full to empty. The austenitic phase material provides superelastic properties corresponding to bending without permanent deformation and permanent strain after load removal (full to empty cycle). The martensite phase material provides super deformable properties, i.e. the ability to undergo large strain and deformation without breaking, and reduces the pressure change applied to the drug held in the drug storage sub-chamber 106. It further provides the advantageous effect of relative flexibility.

  Other materials, such as titanium or tantalum, have excellent biocompatibility and drug compatibility, and can fully accommodate large strain conditions before fatigue properties cause cracks. Although it is preferred to use a superelastic material, titanium or tantalum may be used under certain circumstances. Titanium and tantalum cannot withstand the many cycles available with superelastic materials. However, in such cases, diaphragms made of titanium or tantalum are still applicable in applications where fewer cycles are required. Furthermore, the titanium or tantalum diaphragm 105 is better compatible with the specific composition of the drug.

  [38] The inner wall 102 has an inlet portion 102a in which the partition wall 108 is disposed. The housing 101 has an opening 101 c that allows access to the drug storage subchamber 106 through the partition wall 108. The inlet portion 102 a has a bore 102 b that allows fluid communication into the drug storage subchamber 106. A suitable type of filter, such as a titanium filter 109, is disposed in the vicinity of the outlet 106 a of the sub chamber 106. This filter filters the drug as it leaves the subchamber 106 and enters the flow restrictor 110. The flow restrictor 110 shown in the drawing is a round capillary having an inlet 110a and an outlet 110b. Inlet 110a and outlet 110b may be placed in fluid communication by means well known in the art and each by means described below. The outlet 110b is in fluid communication with a pump outlet 111 having a bore 111a through which the medicament exits the pump 100.

  [39] As shown in FIGS. 1a-1c, 2 and 3, the pump 100 has a height of about 9 mm, a diameter of about 27 mm, and an overall dimension of about 4 cubic centimeters (cc). The pump has a drug storage sub-chamber 106 of about 1 ml. The pump 100 can be as large as about 30 cc and the subchamber 106 can be correspondingly made up to 10 ml, but it is recognized that this is still a small pump.

  [40] Referring now to FIGS. 4 and 5, a second embodiment of the pump 200 is shown. Pump 200 is similar to pump 100, but uses a different flow restrictor. Thus, although only the flow restrictor 210 will be described in detail, it will be appreciated that other components such as the diaphragm 205 are similar. The flow restrictor 210 includes a first coating layer 210a. The second layer 210b includes a constant flow restriction passage and a variable or adjustable passage, and finally the inlet 210c is all retained within this layer 210b. The material for such a flow restrictor 210 can be Pyrex (registered trademark) or flowd glass or titanium. These layers have a flat donut shape.

  [41] In FIGS. 6a and 6b, another embodiment of the pump 300 is shown. Pump 300 is shown to describe flow restrictor 310 in more detail. The drawings do not illustrate some of the component parts of the pump 300, such as diaphragms and portions of other components. However, those skilled in the art will understand how to make such a pump. Pump 300 includes an inner wall 302 having an inlet portion 302a and an outer ring 302b as described above. The flow restrictor 310 is formed by forming a plurality of grooves 312 in the outer ring 302b. The groove is formed by a continuous spiral. The material for the inner wall 302 and the housing 301 can be made of a suitable material such as titanium. Suitable dimensions for the grooves would be about 50 μm wide, 15 μm deep and 100 μm pitch. However, it will be appreciated that other suitable dimensions for the groove may be utilized depending on the desired flow rate. The two parts, the housing 301 and the outer ring 302b, can be suitably connected by means such as heat shrinkage, as will be described in more detail below.

  [42] Referring now to FIGS. 7-11, another embodiment of a pump 1100 is shown. Pump 1100 is similar to pump 200 but uses a different flow restrictor. Thus, although only the flow restrictor 1110 will be described in detail, it will be appreciated that other components such as the diaphragm (not shown) are similar. Pump 1100 is also shown in less detail in FIG. 7, and a portion of flow restrictor 1110 is shown in more detail in FIGS. The flow restrictor 1110 includes a first layer 1112 having an inlet 1112a. On top of the first layer is a second layer 1113, and on top of the second layer is a spiral channel 1113a. A third layer 1114 is disposed on the top and has a plurality of outlets 1114a along with a flow path 1114b. The third layer can be rotated such that a specific outlet 1114a is used. This changes the length of the flow path 1114b, thus creating a different flow rate. The material for such a flow restrictor 1110 can be Pyrex® or fluidized glass or titanium. Possible dimensions for the layers 1112 to 1114 are an outer diameter of 25 mm, an inner diameter of 6 mm and a thickness of about 1.5 mm.

  [43] Referring now to FIGS. 12a, 12b, 13 and 14, another embodiment of a pump 400 is shown. Again, the pump 400 is shown to illustrate a suitable flow restrictor, and thus a number of components within the pump, such as a diaphragm similar to the diaphragm 105, are not shown. The inner wall 402 has a top surface 402a in which a plurality of grooves 402b are formed. Inner wall 402 and housing 401 are formed of a suitable material, such as titanium, while a silicone seal 412 is disposed between top surface 402 a and housing 401. The groove 402b is again a continuous spiral and can have suitable dimensions such as a width of 30 μm and a depth of 15 μm. Chemical etching is one suitable method for forming the trench. As shown in FIGS. 13 and 14, the silicone seal 412 is disposed on the inner wall 402 and heat and / or pressure is applied to partially push the silicone seal 412 into the groove 402b. Depending on the force applied, the amount of displacement of the silicone seal 412 into the groove 402b changes, thereby changing the flow characteristics of the flow restrictor 410.

  [44] The flow restrictor in the pump described above is intended to provide a flow rate of about 1 milliliter (ml) / month. For this reason, an extremely small passage or flow path is desired. In order to realize this, the design described above is used. A more detailed description of the various designs that can be utilized within a suitable flow restrictor is shown in FIGS. 15-47 and described below.

  [45] Overall, the groove is placed on the material layer and then covered with another layer to close the groove and provide the required passageway. The passages can be any number of pattern shapes to achieve the required length. Similarly, one or more passage layers can be combined by the final chip assembly. This general idea can be completed by a combination of groove technology, adhesion and calibration.

  [46] The grooves can be etched by using wet etching methods such as photolithography and chemical etching, deep reactive ion etching (DRIF), ion etching, lithography, electroplating, injection molding (LIGA). it can. The groove can be closed by bonding one layer to the top of the etched layer by using methods such as ionic bonding, diffusion bonding, or by compressing the elastomeric layer to the top of the etched channel. . The size and length of the passage is used to determine the exact limiting effect that is desired to be used to contribute to the overall flow accuracy of the device. In order to achieve an accurate limiting action, the groove dimensions must be controlled to be accurate or the length can be calibrated by one of numerous methods. These methods include the steps of etching with high precision to less than 1 um variation so that no calibration is required. By choosing the appropriate number or location of holes that are plugged to provide a calibrated length, multiple outlets are provided near the end of the length that will be plugged. Including a path that blocks the loop or selected area of the path. Alternatively, during bonding, the depth of the passage is changed or the amount of compression of the elastomer layer covering is changed.

  [47] Referring to FIGS. 15-43, many of these ideas are shown. FIG. 15 shows a groove formed in the outer diameter portion of the inner wall. FIG. 16 is a diagram showing a turn if the outer wall is flat. FIG. 17 shows a conical helix on the inner wall. FIG. 18 discloses a partially flat groove in the inner wall. FIG. 19 discloses a structure in a part using micro laser sintering. FIG. 20 is an example in which there is no central symmetry with respect to the groove. FIG. 21 shows a view in which a titanium sheet has a structure having a plurality of grooves, and is then folded into a conical shape. FIG. 22 is a diagram of a glass capillary as previously shown in FIGS. In this case, the inner diameter of the glass capillary is about 40 μm and the outer diameter is 100 μm. The tube will be cut to a suitable length so that it can be properly calibrated.

  [48] FIG. 23 shows a titanium sheet in which the grooves are formed of a flat sheet and then folded in a spiral. [49] FIGS. 24-28 are diagrams of various techniques for closing or sealing a groove. FIG. 24 shows a view in which the groove and covering parts are assembled into an interference fit using differential heat to achieve an interference fit. FIG. 25 is a diagram showing diffusion bonding. Diffusion bonding is well known and uses heat and pressure. FIG. 26 is an illustration of compressed silicone as shown with respect to FIGS. FIG. 27 shows a strong compression state, and FIG. 28 shows a medium compression state.

  [50] FIGS. 29 to 36 show various groove manufacturing techniques. FIG. 29 shows an electric discharge machine (EDM) technique. FIG. 30 is a diagram of photolithography or chemical etching. FIG. 31 shows deep reactive ion etching and FIG. 32 shows water jet guided laser technology. FIG. 33 shows a lithography electroplating injection molding method (LIGA), and FIG. 34 shows a microlaser sintering method. FIG. 35 shows a glass capillary, and finally, FIG. 36 shows a state where a thin titanium layer is etched on a glass substrate.

  [51] FIGS. 37-43 illustrate a flow restrictor calibration method. FIG. 37 shows a state in which the glass capillary is cut to a desired length. FIG. 38 shows a capillary having a number of outlets, selecting the proper outlet for the correct length, and plugging the other outlets. FIG. 39 shows a state in which the cross section of the groove is changed to change the flow rate (illustrated by a broken line). FIG. 40 is an illustration of a combined system having a length of capillary and a micromachined portion for calibration or adjustment. FIG. 41 shows a state in which the length of the cross section is locally changed. FIG. 42 shows the steps of choosing the correct outlet with the rubber stopper and removing the others. FIG. 43 shows the steps of shortening the length of the passage by closing the passage labeled with x, thereby changing the length.

  [52] It is necessary to have means for connecting the flow restrictor with the inlet and outlet portions of the flow path. The connector can be diffusion bonded or compressed, welded or screwed together with an O-ring or other gasket as shown in FIGS. [53] FIG. 44 to FIG. 47 are diagrams of different connection portions of the flow path. It is necessary to connect the flow restrictor groove to both the sub-chamber holding the drug and the outlet of the pump. FIG. 44 shows a connection 700 having a bore 701 therethrough. The mounting portion is sealed with an O-ring 702. FIG. 45 shows a state in which the mounting portion 800 is welded to thereby form a seal. FIG. 46 shows a state where the insert 900 is diffusion bonded. FIG. 47 is a view of a threaded mounting portion 1000 screwed into a portion that approximates a flow restrictor. An O-ring 1001 is used for sealing. [54] FIGS. 48 and 49 are diagrams of an integral titanium filter that is laser welded as shown in FIG. 48 or press fit as shown in FIG.

  [55] Referring now to FIGS. 50-57, another embodiment of a pump 500 is shown. Pump 500 represents a pump that can be used as a prototype. Thus, particular parts of the structure are shown that are beneficial for prototype design but do not necessarily need to be incorporated into the manufacturing design. Pump 500 includes a suitable housing 501. The housing includes a top half 501 a, a bottom half 501 b, and an inner wall or partition wall 502. The inner wall 502 is operatively connected to the housing and divides the interior of the housing 501 into an upper cavity 503 and a lower cavity 504. A diaphragm 505 is operably connected to the housing and inner wall 502, and the diaphragm 505 divides the lower cavity 504 into a drug storage subchamber 506 and a propellant chamber 507. Again, the diaphragm 505 is a superelastic material such as Nitinol. Although not shown in FIG. 51, the diaphragm 505 can have the same shape as the diaphragm 105 shown in FIGS. The propellant chamber 507 can be filled with a suitable propellant, such as a two-phase propellant, as is well known in the art. A propellant passage 540 is formed in the bottom half 501b and is in fluid communication with the propellant chamber 507. After filling, the gas pin 541 can be inserted into the propellant passage 540 to hold the propellant in the propellant subchamber 507.

  [56] The inner wall 502 has an inlet portion 502a in which the septum 508 is disposed. A septal ring 542 can be utilized and the septum 508 can be disposed therein. The housing 501 has an opening 501 c that allows access to the drug storage subchamber 506 through the septum 508. The inlet portion 502a has a bore 502b that provides fluid communication into the drug storage subchamber 506. A suitable type of filter, such as a titanium filter 509, is positioned proximate the outlet 506 a of the subchamber 506. This filter filters the drug as it leaves the subchamber 506 and enters the flow restrictor 510. The components described above for pump 500 are well known in the art and can be assembled by means that can include welding.

  [57] The flow restrictor 510 is more clearly shown in FIG. 52 and some of its components are shown in FIGS. The flow restrictor 510 is a chip assembly including a first substrate 511 and a second substrate 512. The term chip assembly is used when formed in a manner similar to forming a microchip. The substrates 511 and 512 are preferably glass or silicone. The substrate 511 is a quadrangle as a whole, and has a first planar surface 511a and a second planar surface 511b. The second substrate 512 has a first planar surface 512a and a second planar surface 512b. The planar surfaces 511a and 512a are disposed at positions close to each other. The substrate 511 has a first opening 511c extending from the first surface 511a to the second surface 511b. Similarly, the second opening 511d also extends from the surface 511a to the surface 511b. A continuous passage 512c is micromachined into the surface 512a. The path of the passage 512c is best shown in FIG. 53, and the shape of the passage 512c is best shown in FIG. The passage 512c has a width of 0.02 mm ± 200 nm and a height of 0.005 mm ± 50 nm.

  The passage 512c is separated from the adjacent passage by about 0.1 mm. By changing the size and length of the passageway, the amount of drug flowing through can be changed. The passage 512c provides a flow path for the drug. The holes 511c and 511d are powder blasted. The passage 512c is formed by fine processing. Such microfabrication processes are common in the semiconductor industry as well as in the microfluidic industry. The opening 511c is proximate to the outlet of the drug reservoir 506, and the opening 511d is proximate to the catheter outlet 530. Catheter 531 is operatively connected to and in fluid communication with outlet 530. Two gaskets 513 and 514 are arranged around the substrates 511 and 512. The gasket 513 has two openings 513a and 513b located above the openings 511c and 511d. The gasket 514 is shown as having similar holes. However, the holes are not necessarily required, only to show that the gaskets 513, 514 are identical and need not have additional portions. However, it is understood that the holes need not necessarily be formed in the gasket 514.

  A shim 515 is placed on top of the gasket 514. The flow restrictors are compressed together by screws 519 secured in a boss 520 having a screw to receive screw 519. As described above, FIG. 50 illustrates one embodiment useful for prototyping. For the manufacturing model, the screw 519 may be omitted and the flow restrictor can be formed to be compression fitted and simply placed on the inner wall 502.

  [58] The diaphragms 105, 205, 505 all move from the full position where the diaphragm is located below to the empty position, as shown in the drawing. This provides a larger drug storage subchamber. Next, when the drug is dispensed, the diaphragm “moves on the centerline”. That is, the center moves up with the entire diaphragm until the diaphragm is close to the lower portion of the top halves 101a, 201a, 501a. This will achieve good volumetric efficiency because at least 90% of the drug in the drug storage subchamber can be dispensed.

  [59] The present invention can also be used at multiple locations within the body due to its small dimensions. The pump can be placed almost anywhere in the body, including the skull or chest area behind the ear. The pump will be implanted in close proximity to the desired delivery site.

  [60] In addition to the design ideas described above, other ideas that can be used are ISOMED®, marketed by Medtronic, Inc., by utilizing smaller diameter tubes. ) Includes glass tubes similar to those used in pumps. Alternatively, the micro thread groove may be cut into the cylinder surface and then closed by a similar smooth surface mounted as an interference fit such as hot pressing. The compressed elastomer may cover the machined titanium passage. Metal injection molding methods can also be used. It is also possible to form grooves in titanium or other metal by water jet induction laser cutting. The grooves can be precision machined in titanium or other metal, the grooves can be chemically etched in titanium or other metal, or microlaser sintering methods can be included.

  [61] The present invention is a pump mechanism used in an implantable drug delivery system. The pump has a pump diaphragm that divides the chamber into a drug storage subchamber and a propellant subchamber. The propellant subchamber is configured to accept a suitable propellant. The diaphragm is made of a superelastic metal material. An example of such a material is NITINOL, a superelastic Ni—Ti alloy. In one preferred embodiment, the diaphragm comprises a configuration that allows the diaphragm to extend over the centerline and has a relatively large deflection at minimum stress. An example of such a configuration is a dome shape. It is understood that the infusion device can be either a metered or variable volume pump. The overall size of the pump is 30 cc or less, and preferably about 4 cc. A smaller 4 cc pump will have about 1 ml of drug storage subchamber.

  [62] The infusion device is preferably refillable and includes a fill port in fluid communication with the drug storage subchamber. A septum is disposed in the fill port. In addition, a filter is disposed between the drug storage subchamber and the flow restrictor while the flow restrictor is in fluid communication with the outlet. The septum may be a silicone septum and the filter may be a titanium filter. [63] The infusion device mechanism can include a suitable flow restrictor disposed between the drug storage subchamber and the outlet. Examples of flow restrictors include microfabricated glass or silicone chip assemblies or glass capillaries, micro screws around the housing, multiple multiple exit discs or silicone sealing over the grooves. Again, the pumps and devices described above can be used as non-implantable pumps. [64] Thus, an embodiment of a small pump for drug delivery has been disclosed. [65] Those skilled in the art will appreciate that the present invention can be practiced in embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation.

It is a perspective view which shows 1st embodiment of the pump according to this invention. It is a side view of a pump. It is a top view of a pump. 2 is a cross-sectional view of the pump shown in FIG. FIG. 3 is an enlarged view of a part of FIG. 2. FIG. 6 is a cross-sectional view showing another embodiment of a pump according to the present invention. FIG. 5 is an enlarged view of a part of FIG. 4. FIG. 6a is a perspective view showing another embodiment of a pump according to the present invention with a portion cut away. 6b is an enlarged view of a portion of the pump shown in FIG. 6a. FIG. 6 is a perspective view, partly cut away, showing another embodiment of a pump according to the present invention. FIG. 8 is a top view showing the first layer of the flow restrictor shown in FIG. 7. FIG. 8 is a top view of the second layer of the flow restrictor shown in FIG. 7. FIG. 8 is a top view of the third layer of the flow restrictor shown in FIG. 7. FIG. 11 is an enlarged side view of the layers shown in FIGS. 8 to 10 in an assembled state. Figure 12a is a perspective view, partly cut away, showing another embodiment of a pump according to the present invention. 12b is an enlarged view showing a part of the pump shown in FIG. 12a. FIG. 13 shows a process for manufacturing the flow restrictor shown in FIG. 12b. FIG. 13 is another diagram illustrating a process of manufacturing the flow restrictor illustrated in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. 7 shows an embodiment of a groove arrangement for producing a flow restrictor for a pump according to the invention, such as the pump shown in FIG. FIG. 4 is a diagram of an embodiment showing a groove technique for closing and sealing a flow restrictor used with the present invention. FIG. 4 is a diagram of an embodiment showing a groove technique for closing and sealing a flow restrictor used with the present invention. FIG. 4 is a diagram of an embodiment showing a groove technique for closing and sealing a flow restrictor used with the present invention. FIG. 4 is a diagram of an embodiment showing a groove technique for closing and sealing a flow restrictor used with the present invention. FIG. 4 is a diagram of an embodiment showing a groove technique for closing and sealing a flow restrictor used with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows an embodiment for forming a groove to produce a flow restrictor for use with the present invention. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 6 shows a flow restrictor that utilizes different designs for calibration. FIG. 5 is a diagram showing various embodiments of connections that connect the flow restrictor with the inlet and outlet portions of the flow path. FIG. 5 is a diagram showing various embodiments of connections that connect the flow restrictor with the inlet and outlet portions of the flow path. FIG. 5 is a diagram showing various embodiments of connections that connect the flow restrictor with the inlet and outlet portions of the flow path. FIG. 5 is a diagram showing various embodiments of connections that connect the flow restrictor with the inlet and outlet portions of the flow path. It is a figure which shows embodiment of the integrated filter used with the pump of this invention. FIG. 6 is a diagram showing another embodiment of an integral filter used with the pump of the present invention. It is a disassembled perspective view which shows another embodiment of this invention. It is sectional drawing of embodiment shown in FIG. It is an expanded sectional view of the part shown in FIG. FIG. 52 is a top view of the chip assembly shown in FIG. 50. FIG. 54 is a cross-sectional view taken generally along line 54-54 of FIG. It is an expanded sectional view of a part labeled with X in FIG. FIG. 52 is a top view of the gasket shown in FIG. 50. FIG. 57 is a cross-sectional view taken generally along line 57-57 of FIG. 56.

Claims (16)

An injection device used for discharging a medicine,
a) a housing having a chamber and an outlet;
b) A diaphragm made of shape memory alloy that is operatively connected to the housing and divides the chamber into a drug storage sub-chamber and a propellant sub-chamber, extending over the centerline for greater volumetric efficiency The diaphragm configured as follows :
c) the propellant subchamber configured to receive a suitable propellant;
d) the shape memory alloy selected to have a low bending stress and not to cause a large pressure change in the drug storage sub-chamber;
e) said drug storage subchamber configured to receive a suitable drug and having an outlet in fluid communication with the outlet of the housing;
and f) a flow restrictor having a first end in fluid communication with the outlet of the drug storage subchamber and a second end in fluid communication with the outlet of the housing .   The infusion device of claim 1, further comprising a septum operatively connected to the housing and in fluid communication with the drug storage subchamber. The injection device according to claim 1, wherein the shape memory alloy is manufactured from a Ni—Ti alloy. The injection device according to any one of claims 1 to 3 , wherein the flow restrictor is a micromachined flow resistor, and the micromachined flow resistor is:
a) a first substrate member having a planar top surface;
b) a second substrate member having a planar bottom surface, wherein the second substrate member is disposed on the top surface of the first substrate member to form a chip assembly; ,
c) one of the top and bottom surfaces with machined passages;
d) an injection device comprising an inlet in fluid communication with the outlet of the drug storage subchamber and an outlet in fluid communication with the outlet of the housing.   The injection apparatus according to claim 4, wherein the first and second substrates are glass substrates. 6. An infusion device according to claim 4 or 5 , wherein the passage is dimensioned to provide a flow rate of about 1 ml / month. The injection device according to claim 4, wherein the passage has a width of 0.02 mm ± 200 nm and a height of 0.005 mm ± 50 nm. The injection device according to any one of claims 1 to 7, wherein the injection device is a quantitative type . 9. An infusion device according to any preceding claim , wherein when the drug reservoir is fully dispensed, it dispenses at least 90% of the drug reservoir full.   The injection device according to claim 3, wherein the Ni—Ti alloy is superelastic.   The injection apparatus according to claim 3, wherein the Ni—Ti alloy is superdeformable. The injection device according to claim 1 or 2 , wherein the flow restrictor is a micromachined flow resistor, and the micromachined flow resistor is:
i) a first glass member having a planar top surface;
ii) a second glass member having a planar bottom surface, the second glass member having a bottom surface of the second glass member disposed on the top surface of the first glass member to form a chip assembly;
iii) one of the top and bottom surfaces having a machined passage;
iv) an injection device comprising an inlet in fluid communication with the outlet of the drug storage subchamber and the tip assembly having an outlet in fluid communication with the outlet of the housing. The injection device according to claim 12 , wherein the shape memory alloy is made of a Ni-Ti alloy. 14. The infusion device of claim 3 or 13 , wherein the Ni-Ti alloy is in an austenite phase that provides superelastic properties so that the Ni-Ti alloy accommodates bending. The Ni-Ti alloy, the Ni-Ti alloy, according to claim 3 or 13 in the martensitic phase to provide a superelastic properties to provide the ability to undergo large strain and deformation without breaking Injection device. The injection device according to any one of claims 1 to 15, wherein the injection device is an implantable type.

Images