Patent Application
20120203164
The present invention relates to a device and method for the controlled delivery of a drug to a targeted layer of the skin in a human or animal subject. In particular, the present invention relates to such a device, system and method for selective drug delivery to the cutaneous or subcutaneous layer of skin to enhances the effectiveness of the drug delivery.
Pen injectors are useful when drug delivery by way of injection is required on a regular bases and in particular when the person delivering the drug does note have formal medical training. Such delivery devices are becoming increasingly common amongst those having chronic conditions such as diabetes where self-treatment enables such persons effectively manage their condition.
A non limiting example of usage of such devices is the area of diabetes. Diabetes is a very serious illness affecting millions of people today. In order to survive many diabetic patients require insulin injections to maintain proper blood glucose levels. Such injections of insulin require drug injection systems.
Many medical treatment systems and methods involve drug injection, systems that employ subcutaneous injections of therapeutic fluids, drugs, proteins, and other compounds. Such delivery systems and methods, especially for insulin delivery, may use injection pens to inject insulin to the subcutaneous tissue.
Current insulin injection pens are generally configured to include a disposable insulin reservoir and a disposable needle through which insulin is delivered to the tissue. In most such systems the needle is disposable intended for single dosage, while the insulin reservoir may be used for a plurality of dosages that may span two or three days.
In many instances, the subject requires that the insulin levels be tightly and continuously controlled therefore insulin delivery by way of injection may be required around the clock to ensure proper blood glucose levels.
With such delivery system primarily two types of insulin drugs may be injected. The first is a long acting insulin providing for the basal insulin needed for keeping patient's blood glucose in the desired range between to meals and over night. A second is a rapid acting insulin bolus injection that provides an amount of insulin to offset the rise in blood glucose levels resultant of the ingested foodstuff, for example, carbohydrates.
Many conventional subcutaneous injection devices are incapable of quickly matching or preventing the rise of blood glucose. The delay in such matching is also true in case of the “rapid-acting” insulin. Some of the reasons for this delay include a lag in the absorption of insulin from the injection site and the time it takes for complex insulin molecules to break down into monomers.
Additionally, since blood glucose levels rise shortly following the meal, the delay in matching insulin to the rising levels causes post prandial hyperglycemic events (i.e., when levels of blood glucose are above normal) to occur. Further, occasionally after a certain period of time passes (e.g., 2-3 hours) after a meal, the blood glucose levels drop yet insulin concentrations in the blood rise followed by the peak of the systemic insulin effect and may result in causing hypoglycemic events (i.e., when levels of blood glucose are below normal) to occur. Both hyperglycemic and hypoglycemic events are highly undesirable.
Additionally, since local blood perfusion at the insulin injection region has large variability, depending on the ambient temperature and other parameters, it induces large variations to the delay of the peak of time profile of the insulin action. Those variations in the insulin peak action period further increase the variability in the blood glucose level.
The present invention overcomes these deficiencies of the background by providing a device and method for improved delivery of a drug, for example insulin, by targeting cutaneous and subcutaneous areas of the skin with high blood perfusion so as to improve drug absorption and pharmaceutical profile of the drug. The device and method of the present invention are particularly adapted for drug delivery with a needle based drug delivery devices or catheter based infusion sets, for example a syringe or injection pen, such that the needle depth of penetration is controllable and is oriented parallel to the skin surface allowing one to reach the targeted skin area.
Although the foregoing description of the device and method of the present invention is provided with examples and description relating to diabetes and use of insulin, it is not to be understood that the embodiments of the present invention are limited to use with insulin or for diabetes as a skilled artisan would appreciate that the device and method of the present invention may be extended to other disease states and/or drug both in an acute or chronic forms.
Unless otherwise defined the various embodiment of the present invention may be provided to an end user in a plurality of formats, platforms, and may be outputted to at least one of a computer readable memory, a computer display device, a printout, a computer on a network or a user.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The materials, methods, and examples provided herein are illustrative only and not intended to be limiting. Implementation of the method and system of the present invention involves performing or completing certain selected tasks or steps manually, automatically, or a combination thereof.
The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in order to provide what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.
In the drawings:
The principles and operation of the present invention may be better understood with reference to the drawings and the accompanying description. The following reference labels listed below are used throughout the drawings to refer to objects having similar function, meaning, role, or objective.
10 skin
12 needle based drug delivery device;
14 needle or catheter exit pore
100 drug dosage selector or controller
110 injector—a mechanism to inject predetermined amount of insulin;
120 needle activator—a mechanism to push the needle into the skin at a predetermined time;
130 drug reservoir;
140 needle or catheter;
150 parallel drug delivery skin manipulating element;
200 concentric heater treatment element;
205 innermost ring;
210 intermediate ring;
220 outmost ring;
240, 250 Wires, cables.
Optionally the same method of parallel administration may be utilized for placing an automatic infusion set with drug delivery catheter for administering a drug and/or medicament. For example, an infusion set may be placed by pinching an area of skin 10 and then placing catheter 18 in place to allow for parallel drug delivery.
Optionally a delivery catheter may be provided with a plurality of pores 14 (
Optionally parallel delivery skin manipulating element 150 may be attached to and/or fit and/or integrated and/or otherwise securely coupled with the needle based drug delivery device 12.
Optionally a plurality of optional parallel delivery treatment elements 150 may be interchangeably fit and/or utilized with needle based drug delivery device 12.
Optionally and preferably needle based drug delivery device 12 comprises a dosage selector 100, injector 110, needle activator 120, drug and/or medicament reservoir 130 and needle 140.
Dosage selector 100 most preferably may be provided to select and/or control and/or otherwise adjusting the amount of drug and/or medicament, for example insulin, that is to be injected and delivered through skin surface 10 in a parallel fashion. Optionally dosage selector 100 may be provided in the form of a syringe plunger, or a control dial of an injection pen, or the like device for controlling the amount of drug to be delivered.
Injector 110 most preferably provides a mechanism to controllably inject a predetermined amount of a drug, for example insulin, as defined with dosage selector 100. Optionally injector 110 may be provided in optional forms for example including but not limited to spring based trigger, mechanical based trigger, electronic based trigger, motor based trigger, any combination thereof or the like. Optionally injector 110 may provide for multistage delivery of the dosage selected with dosage selector 100. For example, a dose of 1 ml may be delivered in a single dose or a plurality of sub-dosages while delivering the full 1 ml dosage.
Optionally injector 110 may be manually or remotely controlled. Optionally remote control of injector 110 may for example be provided by wired, wireless, cellular, RF, short range communication, RFID or the like communication device and/or protocol.
Optionally injector 110 may be controlled by interfacing and/or otherwise communicating with an auxiliary device for example including but not limited to a mobile communication device, mobile telephone, computer, PDA, timing device or the like auxiliary device.
Most preferably needle activator 120 may be provided to push and/or otherwise insert needle 140 in a parallel fashion, parallel to skin surface 10 in a controllable manner such that delivery parameters for example including but not limited to timing and/or needle distance may most preferably be controlled.
Most preferably drug and/or medicament stores 130 is provided to store a sufficient amount of drug that is to be delivered with needle 140.
An optional parallel delivery skin manipulating element 150, depicted in
Most preferably skin manipulating element 150 communicates with injector 110 and needle activator 120 to control the depth of needle penetration in the injection area as well as to control the timing of needle 140 activation.
Optionally, parallel delivery skin manipulating element 150 may be further comprise heating element to further improve the absorption of the drug being delivered, for example insulin.
Optionally skin 10 is lifted to a predetermined height by parallel delivery element 150 by means of adhesive tape which may be utilized to attach element 150 to the skin.
Optionally and preferably injector 110 and activator 120 provide a predetermined needle penetration depth and deployment timing based on the size of the skin fold created with parallel skin manipulating element 150.
Optionally and more preferably injector 110 and activator 120 provide dynamic control of needle penetration depth and deployment timing based on the size of the skin fold created with parallel skin manipulating element 150.
Optionally needle penetration depth may be determined to optimize the absorption and pharmaceutical profile of the drug to be delivered. For example, parallel needle based drug delivery device 12 may provide for injecting insulin or any other drug into any required shallow tissue area such as the dermal layer, the fatty layer or any required layer of the skin 10.
Preferably parallel drug delivery skin manipulating element 150, of
Mechanical pinching device 150 of
Optionally arms 152a, 152b, and/or parallel drug delivery skin manipulating element 150 may be further provided with additional treatment elements for improving or otherwise optimizing the absorption and/or pharmaceutical profile of the drug to be delivered; for example including but not limited to heating element, massage element, ultrasound element, chemical element or the like. For example, parallel drug delivery skin manipulating element 150 comprising arms 152a, 152b may further comprise a heating element, as described in
Most preferably the penetration depth of needle 140 may be controlled, for example by injector 110, as previously described, wherein during the needle 140 penetration into a parallel injection site about skin surface 10 the drug dosage may be delivered in at least one or more locations and/or in a multistage manner and/or sequential manner, or trough a plurality of needle pores or the like. For example, a dose of 60 ml, needle 140 may be targeted to injected to a depth of 1.5 mm, where the dose may be delivered at three different depth locations during needle 140 penetration; for example, a first delivery at 0.8 mm 10 ml of the dose, a second delivery of 30 ml at 1.1 mm and a third delivery at 1.5 mm with the remaining 20 ml of the dose.
Optionally a needle array and/or a plurality of needles may be utilized to deliver the drug dose to a plurality of locations about skin surface 10 in a parallel manner.
Optionally the length of the needle in the last description of the pen,
Most preferably parallel injection procedure and device according to optional embodiments of the present invention may be used also to inject a drug into the dermal layer without the drawbacks that were described above that are generally associated with injection into a precise depth into the dermal layer. For example in Mantoux tuberculin test a purified protein derivative is injected into at a shallow angle into the skin surface using a thin needle. The accuracy of this process is important in order not to have false negative test results. Most preferably utilizing the injector described above may allow one to accurately inject the drug into the target tissue with precise and easy method.
The rate of drug absorption to the blood system depends also on the local concentration of the drug, the higher the concentration the slower the absorption. Hence injection of a larger amount of drug will be slowly absorbed compared to the absorption of a smaller amount of drug as it would require a larger amount of interstitial body fluid to dilute it. To overcome this problem optional embodiments of the device and method of the present invention provide for injecting the drug to multiple locations rather than a single location. In some embodiments the drug is injected to different depth by using a mechanism that advances the needle from one depth to another depth while injecting some of the dose to the different depths. This may be done while the needle travels in or out from the skin. Optionally and preferably advancing mechanism may comprise a spring to push the needle with different stops in which another spring may be used to push a certain portion of the drug. Alternatively an electric motor may be used to advance the needle to certain depths and to push pre-determined portion of the drug to the different depths. Optionally the device according to optional embodiment of the present invention may be suited to be embedded in a pen type of injection but could also be used with a syringe. In this case the syringe is inserted into a cylinder that will optionally and preferably push the whole syringe to the predetermined depth and push the syringe cap to deposit a pre-determined amount of drug at pre-determined depths. This way the local amount of the drug will be smaller and could be absorbed faster. Distribution the drug into a larger volume will increase the rate of drug absorption as the drug is diluted by a larger amount of body fluid.
Optionally needle 140 may be provided with a plurality of pores 14 as shown in
Next in stage 703 injection is initiated, for example to apply a local treatment about the injection site for example including but not limited to activating a heating element, applying a chemical, applying a vasodilating agent, massage, piezoelectric element, ultrasound or the like treatment element to enhance drug delivery.
Next in stage 704 a parallel drug delivery skin manipulating element 150 may be activated for example to pinch a skin area about the injection site, as described in
Next in stage 705 needle penetration is activated most preferably parallel to the skin 10 surface at the injection site. Optionally and preferably needle penetration depth is determined so as to optimize drug absorption and pharmaceutical profile. Most preferably needle penetration depth is determined based on the activation and results of the parallel drug delivery skin manipulating element 150, of stage 704.
Next in stage 706 needle penetration is initiated in a parallel manner to the depth determined in stage 705. Finally in stage 707 dosage delivery is provided optionally to a single location stage 707a at the determined depth, or optionally the drug dose set in stage 701 is delivered in a controllable manner about a plurality of injection locations in stage 707b optionally each injection site may be individually with controllable in terms of local dose and depth.
Optionally in stage 712 optional injection treatment elements for example including but not limited to heating, massaging, local administration of vasodialating chemicals or the like.
Next once the dose is set, in stage 713 the drug is delivered through at least one or more delivery catheters. Optionally the dose may be delivered in one location, stage 713a, or multiple locations in stage through a plurality of pores 14.
Optionally next in stage 724 optional injection treatment elements for example including but not limited to heating, massaging, local administration of vasodialating chemicals or the like.
Next once the dose is set and the injection area primed, stage 725 he drug is delivered through at least one or more delivery catheters,. Optionally the dose may be delivered in one location, stage 725a or multiple locations in stage 725b through a plurality of pores 14.
Optionally inner ring 205 may be heated to a temperature that will not damage the drug, the further away rings 220 will heat to a higher temperatures to increase local blood perfusion but still not damage the drug. It is known that the effect of local heat on blood perfusion extends several centimeters away from the heating site.
Optionally and preferably the injected drug is insulin. Optionally and preferably the drug is not injected but infused to the tissue using an infusion catheter.
US patent application US2007000821230, incorporated herein by reference as if fully set forth, describes methods and apparatus for increasing local blood perfusion which improves the delivery into the blood system of a drug injected into the subcutaneous tissue, incorporated herein by reference. The methods described in this patent may be further improved by using modified spatial heating profile. By increasing the heated area around the injection site the effect on insulin absorption into the blood may be increased. For example, the effect of the device on insulin PK was tested by comparing insulin concentration in the blood with and without the device in a meal tolerance test protocol for two different heating pads with different heating areas. It was found that increasing the heating area from 8.2 cm2 to 17.5 cm2 increases the effect of the InsuPatch device on PK profile. The small heating element improved the area under the curve of insulin delivery during the first hour (AUC1 hr) by 30% while the larger heating element improved the AUC1 hr by 45%.
US patent application US2007000821230, herein incorporated by reference as if fully set forth, describes methods and apparatus for increasing local blood perfusion which improves the delivery into the blood system of a drug injected into the subcutaneous tissue. The methods described in this patent may be further improved by using modified temporal heating profile. It is known from the literature that heating the tissue increases local blood perfusion and that this effect stays on even if the heating is switched off for some time.
Using such a heating profile may save power needed to increase blood perfusion. It is known that Laser Doppler (‘LDF’) signal is a marker for cutaneous blood perfusion and may be used to track changes in blood perfusion
In another embodiment all the delivery methods described above are used with the Viaject™ sinulin which is ultrafast insulin drug was developed by Biodel™.
In another embodiment the methods for increasing blood perfusion such as heating massaging and other method listed on US patent application US2007000821230, herein incorporated by reference as if fully set forth, are applied to an insulin injection site where the insulin injected is the Viaject from Biodel. Adding the blood perfusion increasing methods such as heat or massage may help also reduce pain and irritation that may occur in some cases of Viaject insulin injection.
While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications and other applications of the invention may be made.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IB10/54476 | 10/4/2010 | WO | 00 | 4/2/2012 |
| Number | Date | Country | |
|---|---|---|---|
| 61247952 | Oct 2009 | US |
