This filing relates to micro- and/or nano-scale needle (hereinafter “microneedle”) and microneedle array type devices, and more particularly to associated fluid delivery features for forcing liquids (often drugs) through the needle(s) for effective intradermal, subcutaneous or other drug injection.
In the last few decades, the development of new drugs for human use with improved potency has been a focus in the pharmaceutical field. However, the administration of such drugs has been limited due to poor absorption and enzymatic degradation in the gastrointestinal tract as well as painful delivery using intravascular injection.
Microneedle delivery systems offer an attractive option for administering those drugs across the skin. Microneedle use is promising because (typically in an array) such structures can provide holes to bypass the stratum corneum of skin for drug delivery with little or no pain.
The type of microneedles used may be categorized as luminal or dissolvable. Dissolvable microneedles include a polymer tip that dissolves when in contact with body fluid to deliver a drug, vaccine inoculation or other therapeutic agent. As the designation implies, luminal microneedles are bodies that include a lumen therein. The lumen in this class of microneedle may be used to deliver compounds in connection with various reservoir means such as described in U.S. Pat. No. 3,964,482 or U.S. Pat. No. 8,257,324.
Microneedles are sometimes made from stainless steel or other metals; other microneedles are fabricated employing micro-replication techniques, such as by injection molding of plastic material. The resulting products often fail to offer many of the advantages associated with microneedles and microneedle arrays fabricated from carbon nanotubes (CNTs). CNT-based microneedles have unmatched advantages due to their exceptional mechanical properties and simple fabrication processes. Irrespective of the type of luminal micro-needles to be used herein, improvement to the fluid handling hardware feeding the needle array may be of great value as further described.
Micro-needle penetration depth limits associated drug delivery rate and volume. The subject devices, systems and methods involve an injection approach that can generate high liquid speed to increase penetration depth. Another possible advantage is to enable maintaining a high pressure (as discussed further below) through drug (or other liquid) discharge.
Yet another possible advantage is to provide a delay action between the application of pressure by finger and onset of fluid discharge. Still another possible advantage is in providing a system that operates automatically (e.g., for needle insertion and fluid delivery therefrom in the same sense of a device that does once a latch is released) without the sound and/or associated physical force feedback (as in a jerk or rattle) after push-button actuation. These advantages (i.e., delay and/or so-called “automatic” action) may offer a use and/or user adoption advantage(s) in physiologically decoupling a physical actuation (e.g., finger squeeze and depression) from any associated discomfort. As such, a user may not “jump” or “flinch” such as when performing a manual or spring-loaded finger stick procedure. Avoiding such action may help inadvertent disruption of delivery device position and/or microneedle position or engagement. Other related use benefits may be observed as well.
Generally, needle and micro-needle array devices are described in which a shift of fluid volume from a first expansion member position, such as a first balloon, to a second expansion member position, such as a second balloon, drives fluid (often drug) delivery through a lumen of (each) of the needle(s). A single tube may define the balloon sub-system. It may be variously configured as detailed below or otherwise. Devices, overall systems and associated methods of use are also detailed.
The subject devices or systems (filled or unfilled with fluid including any drug), kits in which they are included (with and without assembly), methods of use and/or manufacture are all included within the scope of the present disclosure. Some aspects of the same are described above, and more detailed discussion is presented in connection with the figures below. Other devices, systems, methods, features and advantages of the subject matter described herein will be or will become apparent to one with skill in the art upon examination of the following figures and Detailed Description. It is intended that all such additional devices, systems, methods, features and advantages be included within this description, be within the scope of the subject matter described herein, and be protected by the accompanying claims. In no way should the features of the example embodiments be construed as limiting the appended claims, absent express recitation of those features in the claims.
The details of the subject matter set forth herein, both as to its structure and operation, may be apparent by study of the accompanying figures, in which like reference numerals refer to like parts. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the subject matter. Moreover, all illustrations are intended to convey concepts, where relative sizes, shapes and other detailed attributes may be illustrated schematically rather than literally or precisely. The figures in the form of mechanical drawings or CAD models may, however, provide antecedent basis for any size, shape or relative size or shape ratio limitation that may be claimed.
Various exemplary embodiments are described below. Reference is made to these examples in a non-limiting sense, as it should be noted that they are provided to illustrate more broadly applicable aspects of the devices, systems and methods. Various changes may be made to these embodiments and equivalents may be substituted without departing from the true spirit and scope of the various embodiments. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process act(s) or step(s) to the objective(s), spirit or scope of the present invention. All such modifications are intended to be within the scope of the claims made herein.
Before the present subject matter is described in detail, it is to be understood that this disclosure is not limited to the particular example embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.
All features, elements, components, functions, and steps described with respect to any embodiment provided herein are intended to be freely combinable and substitutable with those from any other embodiment. If a certain feature, element, component, function, or step is described with respect to only one embodiment, then it should be understood that that feature, element, component, function, or step can be used with every other embodiment described herein unless explicitly stated otherwise. This paragraph therefore serves as antecedent basis and written support for the introduction of claims, at any time, that combine features, elements, components, functions, and steps from different embodiments, or that substitute features, elements, components, functions, and steps from one embodiment with those of another, even if the following description does not explicitly state, in a particular instance, that such combinations or substitutions are possible. Express recitation of every possible combination and substitution is overly burdensome, especially given that the permissibility of each and every such combination and substitution will be readily recognized by those of ordinary skill in the art upon reading this description.
Two hardware embodiments are first described. An overview of a first injection or injector device embodiment 100 is shown in
Regarding injector device 100, it includes a body member, in this case with upper and lower portions (e.g., as a base or bottom plate 102 and cover 104). These are connected by optional interface features 106a, 106b and 108a, 108b. Various other snap or press fit features may be employed as may be gluing, chemical or ultrasonic welding, press-fitting or other approaches. These approaches may offer a permanent connection such that all of the resulting device is intended for single use as a disposable. Alternatively, the base or bottom plate 102 and associated components may be set for single use and the top applicator portion (associated with cover 104 or otherwise) reusable base members, cartridges, etc.
In any case, the lower body portion includes base plate 102 and a needle or needle array 110 extending therefrom. The needle(s) are shown in fluid communication with a reservoir 112 held by base plate 102.
Fluid (often an aqueous drug solution) is driven through the needle(s) from reservoir 112 when an adjacent tube 120 section is expanded. A proximal tube portion 122 is shown in an expanded or pre-expanded state defining a first volume. By side-to-side compression at user interface region(s) 130—specifically, finger-depressible elastic buttons 132 filing or occupying windows 134—fluid content at the proximal tube portion 122 is shifted to a distal tube portion 124 (as indicated by dashed line).
Both a proximal end 126 and a distal end 128 of the tube 120 are closed. Plugs 140 may be employed for such purpose or other means (such as sealing by adhesive, welding, etc.).
Other optional device or system features include a guide 142 separating the proximal and distal sections of tube 120 so that discrete fluid volume transfer occurs. Stated otherwise, guide 142 ensures the separation of a first (pre-actuation) volume and first “balloon” position from a second (post-actuation) volume and second balloon position in or of the tube. Other guide features such as body walls 144, 146 may further (or otherwise) constrain volume expansion
Another option is for direct connection of reservoir 112 with tube 120 (as indicated by dashed line connection 114) or other integration of the bodies. Without such connection (or integration) the bodies are separate or separable such as shown in
As with distal section 124, the entire tube 120 may be substantially cylindrical. Or the proximal tube section 122 may be expanded or bulbous in shape as in a so-called “balloon” shape as an expansion member.
As shown in
Such a jet or expulsion of fluid is advantageously characterized by its speed. For example, the expelled or expulsed fluid may vary in speed from about 2 m/s to about 10 m/s and up to about 20 m/s or more by employing different (e.g., thicker and/or higher modulus) tube material selection for greater force or impulse load transfer along with the moving fluid volume. Selection of liquid or high-pressure gas for the fluid may similarly assist in achieving higher jet speeds for injection. For gas as the fluid within tube 120, it may be set to a relatively high internal pressure (e.g., at least 20 psi and upwards of 50 psi, so about 1.5 atm to about 3.5 atm, or more such as up to 60 psi or 4 atm pressure); when provided at such pressures, gasses will transfer along tube 120 faster and/or provide as stiffer, stronger or higher spring rate within the tube. And while liquid may transfer along tube slower, is relatively greater mass can provide greater impulse loading to drive drug jet injection. Furthermore, the incompressibility of the liquid eliminates any spring rate associated with a gas-filled chambers in terms of a so-called “air spring” irrespective of gas composition. Duration of injection flow will vary with the above depending on the volume of liquid in the liquid reservoir and administration pressure.
As with embodiment 100, embodiment 200 in
However, it is contemplated that action of the distal tube portion 124, which expands after proximal tube portion is compressed, may instead drive the needle(s). Such action would be facilitated by a spring-loaded slide or carriage as indicated by double-arrow in the
Regardless, a highly ergonomic and user-friendly injection device or system is provided in which depression of one or more buttons or other user-interface means shifts fluid in a tube 120 from a (proximal) first volume position to a (distal) second to drive fluid (from the tube and/or a reservoir 112) for injection without an abrupt impulse force (such as a tick, click or spring-loaded latch release) noticeable by a user. Nevertheless, the injection pressure and associated injection flow is sustained as further described below.
The subject approach can be modeled as involving two connected elastic balloons (A and B) in a system 210 filled with fluid (be it gas, optionally at a pressure to limit its compressibility or increase its spring rate, or generally incompressible liquid) as illustrated in
Initially, the system is inflated with balloons A and B filled to the degree shown via port 212 or otherwise. Upon sealing the system, balloon B remains minimally inflated until pressure in balloon A reaches a threshold by force supplied thereto by a user through compression action of a finger or hand or otherwise mechanically. Such action is indicated by solid arrows. Balloon B then experiences sudden expansion as indicated by dashed arrows. For gas filled balloons, the delay action (i.e., a delay of expansion of balloon B) is experienced—in part—due to gas compressibility. Upon compressing balloon A, the pressure of gas inside does not immediately increase but instead, the increase will lag the mechanical compression. Another reason for the delay is because the compression does not immediately increase the inner pressure to the critical value to bulge balloon B. Thus, for liquid filling, the delay is weaker (i.e., shorter) as compressibility is negligible, but the time delay to build up pressure is still present.
The so-called “Two-Balloon Problem” (Laplace Law) explains such action.
where S1 and S2 are constants determined for the material, d is balloon thickness, r is balloon radius as it changes and R is balloon radius in relaxed state. This curve is characterized by a peak or spike 220. After reaching this threshold value 222, a region of expansion 224 is experienced by the balloon, even at lower pressure, until the pressure required for further filling climbs again thereafter. Before the pressure reaches the threshold value 222, balloon radius also increases somewhat, but pressure builds up. After this critical pressure is reached, the balloon radius expands faster but pressure actually drops. Accompanying this pressure drop (as is expected to occur in balloon B), a strong impulse (as pressure expected in balloon A is still high) is delivered by balloon B expansion against reservoir 112 for driving fluid (e.g., medicinal fluid) therefrom. Due to the mass of the liquid in the tube (if liquid is selected for the fluid within the tube of the two balloon system), a higher impulse is expected accordingly.
It may also be useful to select a tube material that is highly thermally insulative or insulated so as to avoid any temperature-related decrease of pressure over time associated with a gas (e.g., as related per the Ideal Gas Law) as further explained below. Alternatively, selection of liquid for the fluid internal to the tube can mitigate or altogether avoid such temperature-pressure type effects since very little volume change is experience with temperature variation of many liquids.
In use, when the fluid or “bubble” is shifted from the actuating balloon (i.e., balloon A in the model) to the actuated balloon (i.e., balloon B in the model), the fluid will remain shifted to provide force in connection with the actuated balloon (i.e., balloon B) on the drug reservoir (or as the drug reservoir) until all drug has been released. The so-called bubble does not shift back to its original position without manual actuation. As shown in
In
Such action expands the distal tube volume and/or the fluid reservoir (depending on how the system is configured per example embodiments described above or otherwise) driving treatment fluid injection through the inserted needle to the application site at 308. Accordingly, one method embodiment may involve expelling treatment fluid from an externally pressurized or pushed-on reservoir. Another method may involve expelling treatment fluid directly from an expanded body or reservoir, where treatment fluid is stored in the tube itself. Other approaches (including combined activities) are possible as well. In some embodiments, the transfer or fluid or expansion action at 306 may also drive needle insertion into the skin to an application site at 302′ if not already performed.
As pictured against time axis (t) in
In some embodiments, the user, patient, subject or other individual performs device or system positioning and compression (such as manually with a hand, with a pair of fingers, with a finger and thumb or with a single finger). The method may further comprise the user pushing or inserting the needle or needle array into the skin at or near an application site. Needle insertion may also be performed automatically as a consequence of volume transfer or shift by user actuation as described previously. In any case, the treatment fluid delivered may comprise one or more drugs, medicaments or other substances.
The subject methods, including methods of use and/or manufacture of the hardware described, may be carried out in any order of the events which is logically possible, as well as any recited order of events. Furthermore, where a range of values is provided, it is understood that every intervening value, between the upper and lower limit of that range and any other stated or intervening value in the stated range is encompassed within the invention. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein.
Though the invention has been described in reference to several examples, optionally incorporating various features, the invention is not to be limited to that which is described or indicated as contemplated with respect to each variation of the invention. Various changes may be made to the invention described and equivalents (whether recited herein or not included for the sake of some brevity) may be substituted without departing from the true spirit and scope of the invention, where such changes or substitutions do not compromise the nature of the device or spirit of the concepts described herein.
Reference to a singular item includes the possibility that there are a plurality of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “an,” “said,” and “the” include plural referents unless specifically stated otherwise. In other words, use of the articles allow for “at least one” of the subject item in the description above as well as the claims below. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.
Without the use of such exclusive terminology, the term “comprising” in the claims shall allow for the inclusion of any additional element—irrespective of whether a given number of elements are enumerated in the claim, or the addition of a feature could be regarded as transforming the nature of an element set forth in the claims. Except as specifically defined herein, all technical and scientific terms used herein are to be given as broad a commonly understood meaning as possible while maintaining claim validity. Accordingly, the breadth of the different inventive embodiments or aspects described herein is not to be limited to the examples provided and/or the subject specification, but rather only by the scope of the issued claim language.
This filing claims the benefit of and priority to U.S. Provisional Patent Application No. 62/083,070 filed Nov. 21, 2014, which is incorporated by reference herein in its entirety for any and all purposes.
Number | Date | Country | |
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62083070 | Nov 2014 | US |