(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organization
`International Bureau
`
`( 43) International Publication Date
`25 September 2008 (25.09.2008)
`
`PCT
`
`1111111111111111 IIIIII IIIII 11111 IIIII IIII I II Ill lllll lllll 11111111111111111111111111111111111111
`
`(10) International Publication Number
`WO 2008/114223 Al
`(72) Inventors; and
`(75) Inventors/Applicants (for US only): PESACH, Benny
`[IL/IL]; 18 Shir Hashirim st., 48072 Rosh-ha ayin (IL).
`BITTON, Gabriel [IL/IL]; 621 Hadaf Hayomi st., 97279
`Jerusalem (IL). NAGAR, Ron [IL/IL]; 3 Wissotzky st.,
`62502 Tel Aviv (IL).
`(74) Agent: DR. D. GRAESER LTD.; 13 HaSadna St, PO Box
`2496, 43650 Raanana (IL).
`
`(51) International Patent Classification:
`A61M 5/20 (2006.01)
`A61N 1130 (2006.01)
`
`(21) International Application Number:
`PCT/IB2008/051049
`
`(22) International Filing Date: 19 March 2008 (19.03.2008)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`English
`
`English
`
`(30) Priority Data:
`60/895,518
`60/895,519
`60/912,698
`60/940,721
`11/821,230
`61/008,277
`61/016,571
`61/010,758
`
`19 March 2007 (19.03.2007) us
`19 March 2007 (19.03.2007) us
`19 April 2007 (19.04.2007) us
`30 May 2007 (30.05.2007) us
`21 June 2007 (21.06.2007) us
`18 December2007 (18.12.2007) us
`25 December 2007 (25.12.2007) us
`10 January 2008 (10.01.2008) us
`
`iiiiiiii
`
`(71) Applicant (for all designated States except US): INSU(cid:173)
`LINE MEDICAL LTD. [IL/IL]; 70 Pinksker Street P.O.
`Box 10299, 49002 Petach-tikva (IL).
`
`(81) Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA,
`CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE,
`EG, ES, Fl, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID,
`IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC,
`LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN,
`MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH,
`PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV,
`SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN,
`ZA, ZM,ZW.
`
`(84) Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM,
`ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, Fl,
`
`[Continued on next page}
`
`---iiiiiiii
`== --
`!!!!!!!! -
`--------------------------------------------
`--
`(54) Title: DRUG DELIVERY DEVICE
`
`!!!!!!!!
`iiiiiiii
`iiiiiiii
`
`~
`M
`M
`"'1'
`,-...I
`
`106
`
`FIG. 1B
`
`FIG. 1A
`
`112
`
`····-·1
`
`i
`!
`i 102
`!
`/\
`-~
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`100
`
`,-...I ---QO
`Q
`Q
`M (57) Abstract: The present disclosure presents systems, devices and methods for injection of drugs, substances and/or chemicals to
`0 a patient and for improving their effectiveness once they are injected are disclosed. Additional treatment can be applied to a tissue
`
`: , region on the patient into which a drug (e.g., insulin) is injected, to expose the tissue region to various forms of energy or a substance
`;;, to improve the drug's pharmacokinetic and/or pharmacodynamic profile.
`
`Page 1 of 55
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`WO 2008/114 223 A 1
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`1111111111111111 IIIIII IIIII 11111 IIIII IIII I II Ill lllll lllll 11111111111111111111111111111111111111
`
`FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MT, NL,
`NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG,
`CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
`Published:
`-
`with international search report
`
`before the expiration of the time limit for amending the
`claims and to be republished in the event of receipt of
`amendments
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`Page 2 of 55
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`WO 2008/114223
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`PCT/IB2008/051049
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`DRUG DELIVERY DEVICE
`
`CROSS-REFERENCE TO RELATED APPLICATION
`
`[0001] The present invention claims priority to U.S. Provisional Patent Application No.
`
`60/895,518, filed March 19, 2007, U.S. Provisional Patent Application Serial No. 60/895,519,
`
`filed March 19, 2007, U.S. Provisional Patent Application Serial No. 60/912,698, filed April
`
`19, 2007, U.S. Provisional Patent Application Serial No. 60/940,721, filed May 30, 2007,
`
`U.S. Provisional Patent Application No. 61/016,571, filed December 25, 2007, U.S.
`
`Provisional Patent Application No. 61/008,277, filed December 18, 2007 and U.S.
`
`Provisional Patent Application No. 61/010,758, field January 10, 2008, and U.S. Patent
`
`Application Serial 11/812,230, filed June 21, 2007,, the disclosures of which are
`
`incorporated herein by reference in their entireties.
`
`BACKGROUND OF THE INVENTION
`
`Field of the Invention
`
`[0002] The present invention relates to systems and methods for delivering drugs to a patient.
`
`In particular, the present invention relates to systems and methods for subcutaneous injection
`
`of a medicament and using one or more treatment sources to improve effectiveness of the
`
`injected drugs.
`
`Background of the Invention
`
`[0003] Pen injectors are useful when regular injection by persons without formal medical
`
`training occurs. This is increasingly common amongst those having chronic conditions such
`
`as diabetes where self-treatment enables such persons effectively manage their condition.
`
`Many of the insulin pen injectors are reusable and usually loaded with an insulin cartridge
`
`that may be used for a plurality of injections or for a number of days. Many other diabetic
`
`patients use regular syringe(s) and needles for insulin injection.
`
`1
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`WO 2008/114223
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`PCT/IB2008/051049
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`[0004] Diabetes is a very serious illness affecting millions of people today. Many diabetic
`
`patients require injections of insulin to maintain proper levels of glucose in their blood in
`
`order to survive. Such injections of insulin require drug injection systems.
`
`[0005] 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, or regular syringe. In the conventional insulin
`
`injection pens, the pen includes a disposable insulin reservoir and a disposable needle through
`
`which insulin is injected into the tissue. The needle is a single use needle, while the insulin
`
`reservoir can be used for two to three days. In the conventional insulin injection pens, the
`
`injection is done by attaching the insulin injection pen to the skin at the injection site and
`
`pressing a button that first insert the needle using a spring into the subcutaneous tissue and
`
`then inject the insulin to the subcutaneous tissue.
`
`[0006] In many instances, the patients require insulin injection around the clock to keep
`
`proper levels of glucose in their blood. Two major types of insulin can be injected - a long(cid:173)
`
`acting insulin that provides the basal insulin rate needed for keeping patient's blood glucose
`
`in the desired range between meals and over night and an insulin bolus injection that provides
`
`an amount of insulin for matching a dose of carbohydrates consumed by the patient.
`
`[0007] When patient consumes food, his or her levels of glucose rise. Unfortunately, many
`
`conventional subcutaneous injection devices are incapable of quickly matching and/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.
`
`[0008] Additionally, since blood glucose levels rise shortly following the meal, the delay in
`
`matching insulin to the rising levels causes postprandial hyperglycemic events (i.e., when
`
`levels of blood glucose are above normal) to occur. Occasionally, after certain period of time
`
`passes (e.g., 2-3 hours) after the 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
`
`2
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`WO 2008/114223
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`PCT/IB2008/051049
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`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.
`
`[0009] Thus, it is desirable to provide a system and a method that provides efficient and rapid
`
`injection and absorption of the drug to the patient circulatory system. In particular, it is
`
`desirable to provide a system and a method for injection of insulin to the patient that
`
`improves effectiveness of insulin in the blood to maintain normal levels of blood glucose and
`
`prevent or reduce hyperglycemic and hypoglycemic events.
`
`SUMMARY OF THE INVENTION
`
`[0010] The present invention relate to systems, devices and methods for injecting a drug,
`
`substances and/or chemicals to a patient that further provides a tissue treatment element for
`
`improving the effectiveness of drug delivery upon injection. In some embodiments, the
`
`present invention relates to a device for improving performance of drug delivery in the form
`
`of injection pens or syringes. In general, the present invention's suggested methods and
`
`devices can be used in many drug injection devices, such as injection pen(s), syringe(s), or jet
`
`injector(s), or other injection devices. As such, although the present application discusses
`
`mainly injection pens, it is understood by one skilled in the art that such devices can be used
`
`with any other injection devices. In some embodiments, the present invention provides for a
`
`device that further provides an additional treatment to a tissue region where the drug is
`
`delivered. In some embodiments, the treatment is utilized to improve drug delivery process
`
`by improving the drug's pharmacokinetic and/or pharmacodynamic profile. The treatment
`
`may come in various forms, for example, including analgesic, vasodilator or the like. The
`
`treatment may be any form of treatment that leads to improved vasodilatation of the tissue
`
`being injected, including but not limited to, exposing the tissue region to an energy, radiation,
`
`heat, mechanical vibrations, suction, massaging, acoustic stimulation, electromagnetic
`
`radiation, electric field, magnetic field, electrical stimulation, injection of an additional
`
`substance(s), or any combination of the above to improve the drug's pharmacokinetic and /or
`
`pharmacodynamic profile. Each treatment type may have a separate protocol in order to
`
`evoke the necessary reaction such as vasodilatation or the like.
`
`3
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`[0011] In some embodiments, the present invention provides a needle free drug delivery pen
`
`that is coupled to a treatment element. The treatment element improves the pharmacokinetic
`
`and/or pharmacodynamic properties of the drug that is being delivered to the target tissue
`
`using a fluid jet. The drug delivery injector for administering a drug, for example, insulin, as
`
`a jet nozzle configured for firing insulin in a fluid jet in a configuration and with sufficient
`
`velocity to penetrate tissue of the patient to a delivery site. A drug containing compartment is
`
`associated with the nozzle for containing the drug and feeding the insulin to the delivery
`
`nozzle for injection. A firing mechanism includes an energy source is associated with the
`
`drug compartment for forcing the drug through the nozzle at a sufficient velocity to penetrate
`
`to the target site. In some embodiments, the energy source producing the fluid jet can be a
`
`coil spring, gas spring, or any other spring. A trigger or a dosage release button of the drug
`
`delivery injector is movable by the user and associated with the firing mechanism for
`
`activating the energy source that produces the drug fluid jet by forcing of the drug through
`
`the nozzle once the release button is activated.
`
`[0012] In some embodiments, the applied treatment induces vasodilatation through neural
`
`stimulation of the tissue of the drug injection site. The neural stimulation can be induced by
`
`thermal stimulation and/or mechanical stimulation and/or chemical stimulation. The human
`
`neural response to the thermal stimulation includes several mechanisms such as the
`
`Nociceptive Axon Reflex that induce vasodilatation among other effects.
`
`[0013] In some embodiments, the induced neural response, such as the Nociceptive Axon
`
`Reflex, also induces widening of the capillary pores and increasing the capillary wall
`
`permeability. This effect is also significant for improving the absorption of the drag through
`
`the capillary wall.
`
`[0014] In some embodiments, the applied treatment may lead to a reduction in the variability
`
`of the drug absorption in the blood or lymph system and its local and systemic effects. For
`
`example, heating the tissue region in the vicinity of the area of drug delivery to a preset
`
`regulated temperature during and/or after the drug injection and absorption into the blood
`
`may cause local blood perfusion at that region to become more reproducible and the drug
`
`absorption process more uniform and reproducible as well. Also, by reducing the delay
`
`between drug injection into the tissue and absorption into the blood system, the variability of
`
`drug action induced by the delayed profile can be reduced. In some embodiments, the
`
`temperature of the region adjacent to the injection region can be regulated for longer periods,
`
`but the cost may be the energy source volume and weight. Therefore, for minimization of the
`4
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`WO 2008/114223
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`energy source size, the heating period or heating temporal profile can be optimized in relation
`
`to the period of the drug injection and absorption into the blood. In some embodiments, in
`
`which the treatment utilized is, for example, heat, the drug interaction with the treatment
`
`substance or type will be taken into consideration and can be avoided. For example, a drug's
`
`temperature sensitivity will be accounted for so as to avoid protein denaturisation. Insulin is
`
`a temperature-sensitive protein and to avoid damage to the insulin the treatment protocol,
`
`heating can be limited to ensure the efficacy of the delivered drug. For example, the
`
`treatment protocol may control the temperature or the location of the treatment delivery site
`
`so as to not damage the drug.
`
`[0015] In some embodiments, the neural response that induces vasodilatation is stimulated by
`
`applying a mechanical force in the vicinity of the drug infused region, wherein the force
`
`includes, but is not limited to, one or more of the following: pressure, massage, vibration,
`
`suction and/or any other mechanical stimulation. These tissue treatments or stimulations are
`
`known to stimulate the Nociceptive Axon Reflex as well. Among the advantages of the
`
`mechanical stimulation is the fact that it does not damage the drug, whereas for example
`
`heating insulin above 37°C may cause damage to it. The calibration of the applied
`
`mechanical force may be performed by using one of the procedures discussed above.
`
`[0016] In some embodiments, an additional fluid substance can be combined with the drug or,
`
`alternatively, injected, infused, or topically applied (which may include transdermal delivery
`
`of the drug by permeating through the skin of the patient) to the drug injection site, such that
`
`the additional substance induces neural stimulation that leads to local vasodilatation and/or
`
`increases of the capillary permeability. The substances can include tolazine, naftidrofuryl,
`
`suloctidil, nitroprusside, capsaicin, or any other suitable substance. In some embodiments, an
`
`additional substance may induce vasodilatation and improve blood perfusion in the drug
`
`infused tissue region. For example, capsaicin stimulates a neural response through the VRl
`
`receptor and produces a similar response to thermal neural stimulation.
`
`[0017] The treatment element can be an integral part of the drug delivery injection pen,
`
`according to some embodiments of the present invention. In some embodiments, the
`
`treatment element can be an auxiliary unit that may be interchanged, replaced, or added to an
`
`existing drug delivery injection pen. Such a device can be attached to the drug delivery pen
`
`either during or before the drug injection or applied to the drug injection site afterward.
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`5
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`[0018] The treatment element, according to some embodiments, may be any one or more of
`
`(or a combination of): a heating element, a radiation emitter, a sound transducer, a
`
`mechanical/electo-mechanical vibration device, a light emitting device, and an electrode.
`
`[0019] In some embodiments, one or more of properties relating to the treatment element
`
`may be controlled by a processor in order to achieve a desired response of the tissue region
`
`undergoing drug delivery. Such properties include amplitude, phase, frequency, combination
`
`of excitation sources, relative ratio and timing between various excitation sources, or any
`
`other properties. In some embodiments, the treatment type or sources can be also adjusted
`
`according to chemical and/or physical properties of the drug being delivered. The tissue
`
`response to the treatment element/stimulation enhances the functionality of the injected drug
`
`by enhancing the kinetics of molecular transport from the injection site inside the tissue to
`
`various compartments surrounding the tissue region and to the blood system.
`
`[0020] In some embodiments, a treatment element or device supplying tissue treatment or
`
`stimulation to a tissue region can be configured to monitor and control properties of the
`
`treatment source. For example, controllable properties of a treatment protocol include
`
`amplitude, phase, intensity, frequency, or any other properties. Further control can be gained
`
`by actively monitoring, such that the information is provided to a controller ("controller" or
`
`"processing unit") that uses the information to reduce the variability of the drug
`
`pharmacokinetics. In such embodiments, the device can be configured to monitor properties
`
`of the adjacent tissue, such as local blood perfusion or skin temperature. Based on such
`
`monitoring, the information can be provided to the controller that utilizes the information to
`
`improve pharmacokinetic or pharmacodynamic profile of the drug as well as its performance
`
`and reduce variability of the drug injection process.
`
`[0021] In some embodiments, the present invention's device includes a sensor or other
`
`triggering input mechanism that is configured to prevent deployment of the drug delivery pen
`
`unless certain criteria are fulfilled. Such criteria can include activation of a treatment
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`protocol or element.
`
`[0022] In some embodiments, tissue treatment can be applied simultaneously with each
`
`injection of the drug delivery. In other embodiments, the tissue treatment or stimulation
`
`option may be selected manually by the user. In some embodiments, the user may choose to
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`attach the treatment element to the drug delivery pen. The user can enable or disable
`
`mechanically the automatic application of treatment element. The user can activate the
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`WO 2008/114223
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`treatment device or devices before or after the drug injection to enhance the tissue response to
`
`the injected drug. Such activation can be done by pressing a button or a sequence of buttons
`
`on the drug delivery pen.
`
`[0023] For example, in case of an insulin delivery pen, the pen may have a special button for
`
`triggering a "fast bolus" as compared to regular bolus injection provided by the drug delivery
`
`injection pen. The fast insulin bolus mode can be configured to start one of the above
`
`treatments parallel to the injection of insulin or short time before or after the injection of the
`
`insulin bolus for a given period of time. This improves or modifies pharmacokinetics or
`
`pharmacodynamics of insulin administration, tissue blood perfusion and/or absorption in the
`
`blood of a patient and is highly advantageous when applied in conjunction with high
`
`glycemic index foods. Application of a "fast bolus" may be useful for consumption of high
`
`glycemic index foods, where larger rapid glucose excursions occurs, but also in most of the
`
`cases of using insulin boluses for prandial coverage. In some embodiments, application of a
`
`"fast bolus" can be set as the default mode of the drug delivery pen. In some embodiments,
`
`the user may apply the tissue treatment or stimulation before the meal to further increase the
`
`treatment effect.
`
`[0024] In some embodiments, at least one effect of the treatments is to reduce local irritation
`
`caused by the infused drug or local inflammation reaction caused by the injection. For
`
`example, in case of insulin injection, reducing the period in which the high concentration of
`
`insulin remains in the tissue may reduce irritation that may be caused by insulin. It can also
`
`reduce unwanted effects of the insulin delivery, such as, lipohypertrophy.
`
`[0025] Some embodiments of the present invention also provide methods for improving or
`
`modifying a drug's pharmacokinetic or pharmacodynamic profile in order to reduce time to
`
`peak action in the blood of the injected material by applying a modulation pattern to the
`
`infused drug. With this modulation, the injection drug fluid is slightly moved/pulled in and
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`out of the tissue during or after the drug injection process. In such embodiments, this method
`
`may not require an additional device applied to the skin.
`
`[0026] In some embodiments, the drug delivery pen can mechanically attach a small
`
`disposable device to the skin either before, during or after delivery of the drug. The
`
`disposable device can apply a treatment or treatments using at least one of the following
`
`sources: a heat source (such as a heat resistor), a suction port, for example activated by a
`
`pump, a mechanical vibration source, an ultrasound excitation source, an ultrasound
`
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`transducer, a light source, a massaging element, electromagnetic radiation source, electric
`
`field source, magnetic field source, additional substance and/or a combination of at least two
`
`of sources to improve drug pharmacokinetics. In some embodiments, the small disposable
`
`device can be attached manually either before or after injection of the drug.
`
`[0027] In some embodiments, a device for drug injection includes a disposable injection
`
`needle for injecting drug into tissue, a reusable drug delivery pen for inserting the needle into
`
`the patient skin or subcutaneous layer and for injection of the drug through the needle into
`
`one of the skin and/or subcutaneous tissue layer, a treatment device for applying a specific
`
`treatment or stimulation to the drug injected region in order to improve drug's
`
`pharmacokinetic, pharmacodynamic profile and/or to increase blood perfusion in that region
`
`before, during and/or after the drug injection period to improve drug absorption into the
`
`blood system. The needle can be injected automatically at the target site using an automatic
`
`needle triggering piston or spring. In some embodiments, the needle can be injected at the
`
`target site manually through the action of the user inserting the needle independently.
`
`[0028] In some embodiments, a device for drug injection includes an injection catheter for
`
`insertion into the tissue, a drug injection device for infusing a drug into the injection catheter,
`
`a treatment device for applying a specific treatment or stimulation to the drug infused region
`
`in order to improve, modify and/or stabilize the drug pharmacokinetics, pharmacodynamics,
`
`and/or to reduce variations of the drug absorption into the blood system.
`
`[0029] In some embodiments, a device for drug injection includes at least one of the
`
`following: a display, a button, a memory for boluses, a processing unit, a sensor for skin
`
`properties, a sensor for treatment level, a glucose sensor, a user interface, wireless connection
`
`to a PDA or cell phone for having memory and reminders and remote access to support sites.
`
`[0030] In some embodiments, the device for drug/insulin injection includes a glucose sensor.
`
`The glucose sensor may measure blood glucose level at alternate sites (for example, at sites
`
`with reduced blood perfusion, such as arms and legs). The glucose sensor can be provided on
`
`the opposite side the injection end.
`
`[0031] In some embodiments, the present invention can be configured for a jet injection. Jet
`
`injection involves high pressure injection of material, which obviates the use of needles. This
`
`type of injection mode is also referred to as "needle free" or "needleless" injection. In some
`
`embodiments, the pen injection device can include a jet injection, in addition to or in place of,
`
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`the use of one or more needles. Some examples of conventional needle-free injection
`
`systems include the Medi-Jector VISION® and some products by Antares. Such systems can
`
`be adapted for use with the present invention's jet injection system.
`
`[0032] In some embodiments, the injection device includes a disposable nozzle and a
`
`reservoir having an additional substance. The reservoir is located at the nozzle and the
`
`additional substance is provided in a single use or single dose amount. The reservoir is
`
`located within the body of the device and the nozzle features a connector for fluid or other
`
`communication with the reservoir.
`
`[0033] In some embodiments, rather than disposing a nozzle along with an additional
`
`reservoir, an applicator for an additional substance is provided that is attached to or separate
`
`from the device. The nozzle can be disposed along with a gauge for adjusting the amount of
`
`additional substance to be applied. The applicator may be controlled through a button or
`
`other control component. In some embodiments, the gauge can be configured as a ring that
`
`can be rotated around the applicator button or other control device to adjust the amount that
`
`the button is pressed and/or some function of the other control device and/or to adjust the
`
`dose of applied additional substance.
`
`[0034] In some embodiments, the drug delivery pen can include an adhesive material, such as
`
`a sticker, for assisting the user to create a skin fold for administration of the drug and/or
`
`additional substance.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`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.
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`[0035] Figures lA-E illustrate an exemplary drug delivery pen combined with a mechanism
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`for topical application of an additional substance to the drug injection site, according to some
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`embodiments of the present invention.
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`[0036] Figures 2A-C illustrates an exemplary drug delivery pen combined with a mechanism
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`for topical application of an additional substance to the drug injection site, according to some
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`embodiments of the present invention.
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`[0037] Figures 3A-C illustrates an exemplary drug delivery pen combined with a mechanism
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`for topical application of an additional substance to the drug injection site, according to some
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`embodiments of the present invention.
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`[0038] Figures 4A-D illustrates an exemplary drug delivery pen combined with a mechanism
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`for topical application of an additional substance to the drug injection site, according to some
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`embodiments of the present invention.
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`[0039] Figures 5A-C illustrates an exemplary drug delivery pen combined with a mechanism
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`for application of a treatment element on the drug injection site, according to some
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`embodiments of the present invention.
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`[0040] Figures 6A-C illustrates an exemplary drug delivery pen combined with a mechanism
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`for application of a treatment element on the drug injection site, according to some
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`embodiments of the present invention.
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`[0041] Figures 7 A-C illustrates an exemplary drug delivery pen and cover combined with a
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`mechanism for application of a treatment element on the drug injection site, according to
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`some embodiments of the present invention.
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`[0042] Figures 8A-D illustrates an exemplary drug delivery pen combined with a mechanism
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`for application of a treatment element on the drug injection site, according to some
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`embodiments of the present invention.
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`[0043] Figures 9A-C illustrates an exemplary drug delivery pen combined with a mechanism
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`for application of a treatment element on the drug injection site, according to some
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`embodiments of the present invention.
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`[0044] Figures lOA-F illustrates an exemplary treatment element that may be coupled to a
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`drug injection at the drug injection site, according to some embodiments of the present
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`invention.
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`[0045] Figures l IA-E are block diagrams of exemplary drug delivery devices, according to
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`some embodiments of the present invention.
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`[0046] Figures 12A-C illustrate an exemplary drug delivery pen combined with a mechanism
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`for application of a treatment element on the drug injection site, according to some
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`embodiments of the present invention.
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`[0047] Figure 13 is a flow chart illustrating an exemplary method for controlling temperature
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`of heating that is provided by a treatment element in order to prevent degradation of a
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`temperature sensitive drug.
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`DETAILED DESCRIPTION OF THE INVENTION
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`[0048] The present invention relates to a drug delivery pen or other drug injection devices for
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`the injection of a drug at a drug injection site, where the drug in injection device applies a
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`treatment that can improve injected drug's pharmacokinetic and/or pharmacodynamic
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`properties. The following description will refer to a drug injection pen for illustrative, non(cid:173)
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`limiting purposes, however, as can be understood by one skilled in the art, the present
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`invention is applicable to any other drug injection devices.
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`[0049] Figures lA-C are schematic diagrams of an exemplary drug delivery pen 100 having a
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`treatment element coupled to the delivery pen, according to some embodiments of the present
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`invention. Figures lA and lB depict an exemplary drug delivery pen 100 having a pen shaft
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`110, an injection piston release trigger/button 112 (for actuating a piston pump, for example,
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`within the housing of the delivery pen), a treatment release trigger/button 108 (for actuating a
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`pump for delivering the treatment), a needle opening and a housing 102, treatment delivery
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`openings 104, and a drug dosage selector 106. Figure lA is a perspective view of the drug
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`delivery pen 100. Figure lB is a side view of the pen 100.
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`[0050] The drug delivery pen, for the delivery of insulin, may function as do state of the art
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`drug delivery pens by injecting the selected and determined drug dosage 106 and using
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`injection piston release button 112 to release the piston (not shown) that presses and/or
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`otherwise places pressure on the drug reservoir syringe or vial, for causing injection of the
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`required dosage of drug (not shown) into the targeted area and through needle housing 102.
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`In some embodiments, a fluid jet of the de