INGESTIBLE CAPSULE FOR REMOTE CONTROLLED RELEASE OF A SUBSTANCE
The present invention relates to an ingestible capsule for delivery of a substance e.g. a pharmaceutical drug, to a human or animal. The ingestible capsule comprises a capsule wall structure forming a substantially sealed reservoir or lumen holding the substance. An electrical resonance structure, responsive to microwave electromagnetic radiation, is attached to a first wall portion of the capsule wall structure which comprises a lossy dielectric material. At least a predetermined segment of the first wall portion is heated by received microwave electromagnetic radiation to trig- ger a release mechanism of the ingestible capsule.
BACKGROUND OF THE INVENTION
Ingestible capsules such as pharmaceutical drug capsules with controlled release of a substance held in a capsule reservoir are known in the art. Various kinds of waves have been used or proposed to externally trigger a release mechanism in the drug capsule such as ultrasound, light waves or alternating low-frequency magnetic fields. Suitable antenna structures have been mounted in, or on, the drug capsule for receipt of the relevant type of waves inside the patient's organism. However, the application of ultrasound waves heats organs and tissue of the patient under treatment. Too much heat damages cells and causes burns. Light-sensitive chemical compounds have been developed that react to the presence of (laser) light. The clear disadvantage of the latter concept is that light is only able of penetrating a few millimetres below the patient's skin since light propagation in human tissue suffers from very high losses. Alternating low-frequency magnetic fields are widely used for controlled drug delivery or release. In this connection, the applied magnetic fields are of sufficiently low frequency to be considered de-coupled from the electric field. However, magnetic fields are extremely hard to focus due the low excitation frequency and correspondingly low resonance frequency of the antenna structure attached to the drug capsule. Hence, it is not possible to focus an alternating magnetic field to a specific portion of the patient's body. Furthermore, receipt of the alternating magnetic field also requires a relatively complex electronic receiving circuit mounted inside the drug capsule. The receiving circuit of prior art capsules converts the received magnetic field to a resonating voltage or current signal in the receiving circuit that dissipates power in a resistive heating element.
U.S. 2012/1 16358 A1 discloses an ingestible drug capsule for delivering a pharmaceutical substance. The drug capsule includes a drug compartment with a window. The window is sealed by a foil with an embedded heating wire. The foil breaks along the heating wire when the latter is heated and expels the drug. The foil is made of a material such as LDPE that breaks when heated above a threshold temperature. The heating wire is heated by the supply of an intense electrical pulse supplied by a battery or capacitor of an electronics module inside the drug capsule. WO 2008/059728 A1 discloses a drug capsule for dispensing a medicament to the digestive tract. A permanent magnet based drive system removes a plug that releases the medicament by a dispensing command. The drug capsule comprises an inductor resonator responsive to low-frequency magnetic fields to energize a complex electronic circuit of the drive system that pushes the plug out.
CN 200984246Y discloses an ingestible drug capsule for delivering a pharmaceutical substance to a chosen location in the alimentary tract of humans. The drug capsule includes a receiving circuit for receipt of applied electromagnetic radiation for remote control of drug release. The receiving structure may include a coiled cou- pling antenna embedded in an outer cylindrical wall structure of the drug capsule. The frequency of the applied electromagnetic radiation is specified as larger than 100 kHz. The drug release mechanism includes a movable piston arranged in a cylindrical drug reservoir inside the drug capsule and locked by a low melting point polymeric wire. A micro-thermal resistor, coupled to the receiving circuit, is heated by the received electromagnetic radiation and is operative to melt the locking wire which in turn releases the movable piston and expels the drug.
U.S. 6,632,216 B2 discloses an ingestible drug capsule for delivering a pharmaceutical substance to a chosen location in the gastrointestinal tract (Gl tract) of humans. The drug capsule includes a receiving structure for receipt of electromagnetic radiation for remote control of drug release. The receiving structure may include a coiled antenna wire including 60-100 turns and embedded in an outer cylindrical wall structure of the capsule as illustrated. The frequency of the applied electromagnetic radi- ation is specified as limited to the range 1 -14 MHz. The drug release mechanism includes a movable piston arranged in a cylindrical drug reservoir inside the drug capsule and locked by a thread of sharp melting point material. A resistor heater is heated by the received electromagnetic radiation and is operative to melt the thread which releases the movable piston and expels the drug.
Hence, it would be highly desirable to provide a source of wave radiation with sufficient focusing capability to allow selective irradiation of a specific target area or volume of the patient's body. In this manner, release of the drug or other substance from the drug capsule can be confined to a specific region of the patient's body and be released to the target volume at a desired point in time. The radiation should preferably be capable of penetrating deeply into the patient's body with sufficient strength to be picked-up by a practical antenna structure on the drug capsule and trigger drug release. It would desirable provide an antenna structure which is responsive to microwave electromagnetic radiation to reduce the size of the antenna structure and thereby reduce dimensions of the controlled release ingestible capsule. It would likewise be desirable to eliminate complex electronic circuitry inside the drug capsule and eliminate the need for energy storage devices such as batteries and capacitors associat- ed with energizing heating wires.
The present invention addresses these problems and numerous others as described in further detail below. SUMMARY OF THE INVENTION
A first aspect of the invention relates to an ingestible capsule for delivery of a substance to a human or animal. The ingestible capsule comprises:
-a capsule wall structure forming a substantially sealed reservoir or lumen holding the substance, an electrical resonance structure attached to a first wall portion of the capsule wall structure and responsive to microwave electromagnetic radiation by generation of an alternating electric field,
the first wall portion comprising a lossy dielectric material absorbing energy from the alternating electric field to heat at least a predetermined segment of the first wall portion,
a release mechanism responsive to a predetermined temperature increase of the predetermined segment of the first wall portion. In the present specification the term 'microwave electromagnetic radiation' refers to electromagnetic waves with a frequency above 100 MHz. In the frequency range above 100 MHz, the magnetic field and the electric field become coupled which is a property that allows focusing of the emitted microwave electromagnetic radiation to particular portions of the patient's body by appropriate interference mechanisms. The interference may be accomplished by emitting microwave electromagnetic radiation from two or more cooperating transmitting antennas with appropriate phase relationship.
The focusing capability of the microwave electromagnetic radiation utilized in ac- cordance with the present invention and the responsiveness of the electrical resonance structure thereto allow selective irradiation of a specific target area or volume of the patient's body from remotely located microwave transmitting antenna structure^). In this manner, the controlled release of a pharmaceutical agent, drug or other substance can be confined to the target volume of the patient's body such as a particular portion of a gastrointestinal tract. The release of the pharmaceutical agent, drug or other substance can furthermore be accomplished externally or remotely at any desired point in time by applying the microwave electromagnetic radiation. The substance may comprise a pharmaceutical drug in solid, liquid or powder form. The substance may also be held in a plurality of smaller containers.
The skilled person will understand that the first wall portion of the capsule wall may be a lid, side wall, bottom portion or any other suitable wall portion of the capsule wall structure possessing sufficient dimensions to support the electrical resonance structure. The skilled person will appreciate that the term 'ingestible' as utilized herein means that the drug capsule is shaped and sized such that the capsule can be swallowed by a human or animal. The skilled person will appreciate that the ingestible drug capsule therefore in some embodiments may be sufficiently small to allow injection into the bloodstream of the human or animal, e.g. a patient undergoing a medical procedure. In the latter embodiment, the pharmaceutical agent or drug may be con- trollably released near or inside selected organs or target objects (e.g. a cancerous tumour) of the patient under treatment.
In accordance with the present invention, the first wall portion comprises a lossy dielectric material. This lossy dielectric material is arranged to absorb energy from the alternating electric field generated in the electrical resonance structure in response to receipt of the microwave electromagnetic radiation, in particular micro- wave electromagnetic radiation located at or close to a resonance frequency of the electrical resonance structure. The alternating electric field induces electric currents in the predetermined segment of the first wall portion due to its electric conductance as described below. The electric currents cause power loss in, and heating of, the predetermined segment. Depending on the shape and size of electrical resonance structure the predetermined segment may comprise smaller or larger area of the first wall portion. In some embodiments, the predetermined segment is essentially confined to one or more gaps in the electrical resonance structure attached to the first wall portion. The direct heating induced by the electrical resonance structure of the lossy dielectric material of the capsule wall of the ingestible capsule in response to externally applied microwave electromagnetic radiation eliminates the need of electronic RF receiving circuits, electronic components and energy storage devices like batteries or capacitors as widely used in prior art devices as previously described. This fea- ture leads to significant size and costs reductions, simplification of electric circuitry, improved reliability, removal of patient safety concerns and other benefits in the present ingestible capsule.
In the present patent specification the term 'lossy dielectric material' refers to a material with a specific electrical conductance, σ, between 0.01 and 1000 Sm" , more preferably between 0.02 and 10 Sm~\ and even more preferably between 0.05 and 0.2 Sm"1 , at a frequency of operation such as at the resonance frequency of the electrical resonance structure . Preferably, the lossy dielectric material possesses in addition a relative permittivity, er, between 1 .0 and 80 such as between 2.0 and 15, at the frequency of operation. Experimental results obtained by the present inventor suggest that these ranges of electrical conductance, σ, of the lossy dielectric material enable the alternating electric field to dissipate sufficient power in the lossy lid material to produce useful temperature increases for triggering the release mechanism as described below in additional detail.
The lossy dielectric property of the substrate or base material may be achieved in numerous ways. In one embodiment, the base material comprises a bio-degradable polymer mixed with a conductive powder, such as a metallic powder, of sufficient density to reach the above-mentioned preferred ranges of specific electrical con- ductance of the lossy dielectric material. Other types of bio-degradable dielectrics or semiconductors doped with materials which increase or decrease the electric conductivity such that the resulting conductivity falls within the above specified ranges could also be used. According to a preferred embodiment, the polymer comprises a bio-compatible polymer, preferably a temperature sensitive bio-compatible polymer, which abruptly changes its chemical or mechanical properties within a predetermined temperature span such as a span less than 10, 5 or 3 °C. The chemical or mechanical properties that changes within the predetermined temperature span may be properties like ad- hesion, viscosity or permeability. In one preferred embodiment, the polymer may comprise a semi-crystalline graft copolymer (Intelimer®).
The temperature increase induced in the predetermined segment of the first wall portion may trigger the release mechanism in various ways. In a number of useful embodiments, the release mechanism comprises a transition of the predetermined segment of the first wall portion from a first chemical state to a second chemical state or a transition from a first mechanical state to a second mechanical state. The transition from the first to the second state takes place within a predetermined temperature span such as a temperature span of less than 10 °C, or less than 5 'Ό, or even more preferably less than 3 °C. In these embodiments, the temperature increase leads to a change of the chemical or mechanical state or property of the segment itself. In the manner, the release mechanism is directly triggered by the heating of the predetermined segment of the first wall portion. The transition be- tween the first and second states of the predetermined segment of the first wall portion may include a change to numerous physical properties like adhesion, viscosity, state (e.g. from solid to liquid) or permeability etc.
In a number of alternative and likewise useful embodiments, the temperature in- crease in the predetermined segment of the first wall portion is conveyed by thermal coupling to a separate release mechanism. In one such embodiment, the separate release mechanism comprises a structure thermally, coupled to the predetermined segment of the first wall portion, transiting from a first chemical state to a second chemical state or transiting from a first mechanical to a second mechanical state. In one such embodiment, a layer of a temperature sensitive adhesive agent is interposed between the first wall portion and the residual capsule wall structure to firmly bond these at room temperature and at temperatures up to about 37 °C. The bond between the temperature sensitive adhesive agent and the first wall portion couples these thermally. The temperature sensitive adhesive agent has a melting point sev- eral degrees above 37<Ό for example around 40 °C. In effect, the bond between the above-described wall structures of the ingestible capsule is released by the melting of the temperature sensitive adhesive agent once the temperature thereof exceeds 40 °C and the substance captured or enclosed in the ingestible capsule released. The skilled person will understand that the first wall structure may comprise a lid, sidewall or bottom portion of the present ingestible capsule.
The electrical resonance structure functions as a receiving antenna for the microwave electromagnetic radiation emitted by the above-described transmitting antenna structure. The electrical resonance structure may be shaped and sized in numerous ways to efficiently receive the microwave electromagnetic radiation above 100 MHz. The electrical resonance structure is preferably shaped and sized to provide a resonance frequency higher than 100 MHz, preferably in the range 300 MHz - 3 GHz, such that the frequency of applied microwave electromagnetic radiation can be tuned to the selected resonance frequency and the previously described focusing capability of electromagnetic waves in this frequency range exploited.
According to one embodiment, the electrical resonance structure comprises a metal- lie loop structure with one or more gap(s). The metallic loop structure tend to focus the alternating electrical field across the gap(s) such that the above-discussed predetermined segment of the first wall portion can be efficiently heated by arranging the segment in the gap(s), or at least proximate to the gap(s). Furthermore, the electrical resonance structure may be formed as a substantially flat metallic structure deposited on the first wall portion of the ingestible capsule such that any space occupation can be largely neglected. The maximum dimension will vary depending on the selected resonance frequency of the metallic loop structure, but may be less than 15 mm such as between 0.2 mm and 10 mm. In a particularly useful embodiment of the electrical resonance structure, the metallic loop structure comprises a split-ring resonator. Split-ring resonators are very compact resonance structures and typically resonate when an electrical size of the structure is less than λ/10 (λ being the wavelength of the microwave electromagnetic radiation in the first wall material (in comparison to typical microwave resonance structures or antennas that resonate at wavelengths of the electrical size of λ/2. The small electrical size of split-ring resonators makes these highly advantageous as receiving antennas in the present ingestible drug capsule compared to λ/2 antenna structures because dimensions of the electrical resonance structure, and thereby dimensions of the ingestible drug capsule, are markedly smaller for a given reso- nance frequency. Or stated in an alternative way, for a given size of the ingestible drug capsule, the frequency of the applied microwave electromagnetic radiation can be significantly lowered which enables deeper penetration into the patient's body
The split-ring resonator may comprise one or more gaps and generally exhibit nu- merous different more or less complex shapes such as those depicted in the accompanying figures. The split-ring resonator preferably comprises at least two curved and substantially continuous metallic strips or traces each interrupted by a short gap, i.e. each strip possessing a semi-closed shape. In one embodiment, the split-ring resonator comprises a pair of co-axially arranged loops of metal. The pair of loops may in principle have an arbitrary shape for example substantially rectangular, oval, circular etc. In one embodiment, the pair of co-axially arranged loops comprises an inner substantially circular ring with a first gap arranged therein and an outer substantially circular ring with a second gap arranged therein. The first and second gaps are rotationally displaced relative to each other by an angle of about 180 degrees. The height of each of the first and second gaps may lie between 0.01 mm and 0.75 mm, such as between 0.1 mm and 0.5 mm, depending on the maximum dimension of the resonator structure. In another embodiment, the electrical resonance structure is formed as a substantially flat spiral conductor structure com- prising a largely continuous gap formed between facing edges of individual revolutions or arms of the spiral.
In a preferred embodiment of the present ingestible capsule, the predetermined segment is formed as a bridge structure interconnecting otherwise unattached areas of the first capsule wall portion. The bridge structure is placed in the gap of the electrical resonance structure such that the bridge becomes heated and melts or dissolves by the temperature increase. In one such embodiment, the segment of the lossy dielectric material forms a bridge between an inner unattached part of the first capsule wall portion arranged inside the electrical resonance structure and an outer attached part of the first wall portion arranged outside the electrical resonance structure. Hence, in the latter embodiment the melting of the bridge detaches the inner unattached part of the first capsule wall portion to open up the sealed reservoir or lumen of the ingestible capsule and release the substance held therein. To reach practical dimension of the present ingestible capsule there are limits to the maximum dimensions and form of the capsule wall structure. The constraints of the capsule dimensions depend on the particular application in question and naturally also impose certain restrictions on the maximum dimension and shape of the electrical resonance structure. In a number of useful embodiments, the electrical reso- nance structure is formed as a substantially flat structure having a maximum dimension less than 15 mm.
A second aspect of the invention relates to a method of delivering a substance held in a ingestible capsule according to any of the preceding claims to the alimentary canal of human or animal. The method comprising steps of:
a) causing the human or animal to ingest the ingestible capsule,
b) placing the human or animal in predetermined location of a support,
c) generating microwave electromagnetic radiation by a microwave antenna struc- ture,
d) adjusting an excitation frequency of the microwave electromagnetic radiation to a resonance frequency of the electrical resonance structure attached to the wall structure of the ingestible capsule,
e) directing the microwave electromagnetic radiation to a target portion of the ali- mentary canal to heat at least the predetermined segment of the first wall portion and increase the temperature of the lossy dielectric material to trigger the release mechanism. The excitation frequency of the microwave electromagnetic radiation is preferably larger than 100 MHz for the reasons discussed above. BRI EF DESCRI PTION OF THE DRAWINGS
Preferred embodiments of the invention will be described in more detail in connection with the appended drawings, in which:
FIG. 1 illustrates schematically a system for controlled release of a substance held in an ingestible capsule,
FIG. 2 is a 3D perspective view of an ingestible drug capsule in accordance with a first embodiment of the invention,
FIG. 3A) is a schematic top view of the lid of the pharmaceutical drug capsule depicted on FIG. 2 illustrating geometry of the electrical resonance structure according to the first embodiment of the invention,
FIG. 3B) shows simulated power loss density across a surface of the lid of the pharmaceutical drug capsule for the case of maximum temperature increase as illustrated in FIG. 4A),
FIG. 4A) is a graph depicting maximum temperature as a function of specific electrical conductance for a wide range of conductivities of the lid material of the pharma- ceutical drug capsule depicted on FIG. 2, for relative permittivities of 3 and 6,
FIG. 4B) is a graph depicting the same variables as FIG. 4A) but zoomed to a narrow range of values of the specific electrical conductance of the lid material, for relative permittivities 1 .5, 3, 6 and 12, FIG. 5) is a side perspective view of the lid of the pharmaceutical drug capsule depicted on FIG. 2 with dimensions of the electrical resonance structure added; and FIGS. 6A) and 6B) are respective schematic top views of alternative electrical resonator designs.
DETAILED DESCRI PTION OF PREFERRED EMBODIMENTS
FIG. 1 illustrates schematically a set-up or system allowing externally controlled release of a pharmaceutical drug or other substance from ingestible drug capsules 102 held in the alimentary canal of a patient. In practice, the patient subjected to the treatment procedure may be fixed at a predetermined location such as arranged on an examination table or bed. The fixed placement of the patient ensures that applied microwave electromagnetic radiation is directed to the target or intended portion of the alimentary canal. The overall procedure comprises steps of causing the patient ingest a plurality of the ingestible capsules or containers 102. Thereafter, the patient is placed at a predetermined location of a support as explained above. The support may be placed between a pair of cooperating microwave antenna structures 108a, 108b that each emits directive microwave electromagnetic radiation as schematically illustrated by directivity patterns 1 10a, 1 10b. The distance between the patient and each of the microwave antenna structures 108a, 108b may lie between 1 and 3 meters under typical circumstances but may be smaller or larger in other situations.
A first and a second RF source 104a, 104b, respectively, supply the respective RF signals to the microwave antenna structures 108a, 108b which emits the resulting microwave electromagnetic radiation towards the target area of the patient's alimentary canal (not shown). The patient's alimentary canal comprises the schematically illustrated upper and lower volumes 107, 106 wherein the upper volume is the target area for drug delivery in the present example. In the present embodiment, the excitation frequency of the microwave electromagnetic radiation has been set to about 1 .8 GHz which matches the resonance frequency of the electrical resonance structure attached to, or integrated with, of the ingestible drug capsule (refer to FIG. 2). Furthermore, by adjusting a phase between the RF signals, the constructive interference pattern of the microwave antenna structure can be adjusted. The external excitation antenna(s) should be designed to accommodate for transmissions of electromagnetic waves at the resonance frequency of the chosen electrical resonance structure(s) on the ingestible capsule wall structure. As mentioned above, each of the ingestible capsules 102 comprises one or more miniscule electrical resonance structure(s) (attached to a lid and/or other capsule wall structure(s). The miniscule electrical resonance structure(s) functions as receiv- ing antenna(s) for the applied microwave electromagnetic radiation as described in further detail below. By directing the microwave electromagnetic radiation 1 10a, 1 10b to the target volume or portion 107 of the alimentary canal, a substantial alternating electric field is generated in each of the electrical resonance structures of the capsules 102 held in the target volume. The electrical field increases the tempera- ture of selected segments or portions of a lossy dielectric material which functions as a base material of the lid (212 of FIG. 2) as explained in additional detail below. The heating of these selected segments or portions of lid triggers a release mechanism of the capsule 102 which opens the lid and frees the encapsulated drug to the patient's organism in the target volume 107. On the other hand, lids of the ingestible capsules 102 held outside the target volume, e.g. within the illustrated volume 106, are not heated in any noticeable manner, or least not enough to trigger the release mechanism, due to the lower intensity of the microwave electromagnetic radiation 1 10a, 1 10b in this volume. Hence, the applied microwave electromagnetic radiation is focused at the desired target volume of the patient allowing a selective and re- motely controlled activation of the ingested drug capsules 102.
FIG. 2 is a schematic 3D perspective view of a single one of the above-described ingestible drug capsules 102 in accordance with a first embodiment of the invention. The ingestible drug capsule 102 comprises a capsule wall structure 202 forming a substantially sealed reservoir or lumen holding the substance 204 that is intended for delivery a human or animal. The capsule wall structure 202 accordingly forms the exterior barrier of the ingestible drug capsule 102 and should preferably be shaped and sized to allow trouble free ingestion by patients. The substance comprises a drug in solid, liquid, gaseous or powder form in the present embodiment of the in- vention. The skilled person will understand that numerous other types of substances may be held in the drug capsule. The capsule wall structure 202 comprises a lid 210 that forms a first wall portion of the capsule wall structure. The lid 210 comprises an attached split-ring resonator comprising pair of co-axially arranged substantially annular rings or loops 206, 208 of metal, preferably essentially non-magnetic metal. The split-ring resonator comprises an inner substantially annular ring 208 with a first gap 209 arranged therein and an outer substantially circular ring 206 with a second gap 207 arranged therein. The first and second gaps 207, 209 are rotationally displaced relative to each other with an angle of about 180 degrees.
The split-ring resonator functions as an antenna structure that is receptive to externally applied microwave electromagnetic radiation in a certain predefined frequency range or band. In the present embodiment, the dimensions of the split-ring resonator are chosen such that the above-mentioned resonance frequency of 1 .8 GHz is achieved as described below in additional detail. Split-ring resonators are very com- pact electromagnetic wave resonance structures and typically resonate when an electrical size of the structure is less than λ/10 in comparison to typical microwave resonance structures or antennas that resonate at the electrical size of λ/2. The small electrical size of split-ring resonators makes these highly advantageous for application in remote drug capsule activation compared to λ/2 antenna structures because dimensions of the electrical resonance structure, and thereby dimensions of the ingestible drug capsule, are markedly smaller for a given resonance frequency the electrical resonance structure. Or stated in an alternative way, for a given size of the ingestible drug capsule, the frequency of the applied microwave electromagnetic radiation can be significantly lower which enables deeper penetration into the patient's body.
The split-ring resonator is firmly attached or bonded to an outer surface of the lid 210 for example by an adhesive agent or by soldering etc. In one embodiment, the split-ring resonator may be fabricated by applying UV lithography and etching tech- niques to a suitable substrate material covered by a thin metallic layer. The substrate or base material of the lid comprises a lossy dielectric material with a specific electrical conductance, σ, between 0.01 and 1000 Sm-1 , more preferably within a range between 0.07 and 0.12 Sm" for the reasons discussed below in additional detail. The lossy dielectric property of the substrate or base material may be achieved in numerous ways. In one embodiment, the base material comprises a biocompatible temperature sensitive polymer mixed with a conductive powder of sufficient density to reach the above-mentioned preferred ranges of specific electrical conductance. The temperature sensitive polymer may be a semi-crystalline graft copolymer (Intelimer®) which abruptly changes its chemical or mechanical proper- ties like adhesion, viscosity or permeability, in response to a predetermined temperature increase. In one embodiment, the temperature sensitive polymer changes its adhesion within a temperature span less than 3 degree 'Ό starting with strong adhesion below a temperature of 37<Ό. The adhesive characteristics of the lid material changes from very strong below a temperature of 37<Ό to very weak at or above 40 'Ό such that a bond between the lid 210 and the residual capsule wall structure 202 along the lid edge 206 is dissolved or eliminated and the lid 210 released. In another embodiment, the release mechanism comprises a lid, or other capsule wall structure, with a temperature dependent porosity. In this embodiment, the lid exhibits a porosity capable of withholding the pharmaceutical substance at a temperature at and below 37<Ό, but unable to do so at a higher temperature such as 40 'Ό. The porosity of the porous lid material increases markedly above 40 °C and the pharmaceutical substance is released from the capsule. In response to exposure to the applied microwave electromagnetic radiation 1 10a, 1 10b at, or close to the, resonance frequency of the split-ring resonator, a strong alternating electric field is generated in the gaps 207, 209 of the annular rings or loops 206, 208 and in a separation between them. Due to the lossy property of the lid base material, the strong alternating electric field induces electric currents in se- lected portions or segments of the lid 210 where part of these currents are converted into power loss as illustrated by the power loss density map of the lid 210 on FIG. 3B. This power loss causes an overall increase of the temperature of the lid 210, and a particularly pronounced temperature increase in the lid segments in and close to the gaps 207, 209.
FIG. 3A) is a schematic top view of the lid 210 of the pharmaceutical drug capsule 102 depicted on Figs 1 and 2 for the purpose of cross-referencing the geometry of the electrical resonance structure with the simulated power loss density in FIG. 3B). FIG. 3B) shows the simulated power loss density across the lid surface for the case of maximum power dissipation as discussed in additional detail below in connection with FIG. 4A). The power loss density is mapped on a grey-black scale wherein completely black correspond to a power density on or above 100000 Wm"3 The lightest discernible grey scale value corresponds to a power density about 17000 Wm"3 It is evident that maximum power density is reached in the lid segments in or close to the gaps 207, 209 such that the largest temperature increase of the lid structure 210 therefore occurs at these locations as well.
FIG. 4A) is a graph depicting the simulated maximum temperature of the lid 210 of the pharmaceutical drug capsule depicted above on Figs. 2 and 3 as a function of specific electrical conductance , σ, of the lid base material for two different relative permittivities, er, of the lid material, as determined at the resonance frequency of the resonating structure. The depicted temperature behaviour of the drug capsule was analysed in the 3D electromagnetics (EM) simulation tool CST. Simulations of the optimal specific electrical conductance or conductivity for a given relative permittivity were performed in CST to find optimal parameters for the substrate material for inducing maximum temperature increase in the lid. CST was used for calculating the current- and power loss densities in the lid base material or substrate. These power loss densities are used as sources from which CST calculates thermal losses and the accompanying local lid temperature increase with a surrounding ambient air temperature of 37 °C.
For these simulations, the applied electromagnetic radiation was transmitted from a distance of 25 mm resulting in a 100 V/m plane wave, with an E-field component oriented across to the gaps 207, 209 of the spilt-ring resonator and an H-field component oriented normal to the lid 210. All relevant measurement parameters were kept constant throughout the simulation except for the relative permittivity and specific electrical conductance. The maximum temperature point of the lid substrate at each combination of relative permittivity, er, and relative specific electrical conduct- ance, σ, at the resonance frequency of the spilt-ring resonator is taken. The resonance frequency of the spilt-ring resonator was located at 1 .8 GHz for the present design as previously mentioned.
The upper unbroken temperature curve depicts simulated maximum temperatures for the condition er = 3 and the dotted curve the same quantity for er = 6. The maximum temperature was found to be approximately 41 .5 °C for a lid base material with er = 3 and σ = 0.07 S/m at the resonance frequency of 1 .8 GHz. As indicated by the depicted temperature curves, substrate materials which are too conductive, i.e. having a large specific electrical conductance such as above 1000 S/m (Sm~1), tend to short-circuit the split-ring resonator (receiving antenna) and eliminate any resonance therein. On the other hand, lid materials that have very small specific electrical conductance dissipate very little power as indicated by the depicted temperature curves which rapidly approach 37 °C (no heating) for specific electrical conductance below approximately 0.01 Sm"1. Consequently, it is evident that the optimal range for the specific electrical conductance of the lid material in the present embodiment lies approximately between 0.01 and 1000 Sm"1 which can been seen as an intermediate electrical conductance range in-between the conductance of good conductors (like copper with about 6*107 Sm"1) and bad conductors (like rubber with 10"14 Sm"1). Lid materials exhibiting specific electrical conductance within the latter range can accordingly be considered lossy dielectric materials in the present context. This electrical conductance or conductivity range lies furthermore outside the specific electrical conductance provided by substrates utilized in ordinary printed circuit technology. These are generally based on relatively low-loss substrates like glass- epoxy, ceramics, etc.
FIG. 4B) is a graph depicting a simulated maximum temperature of the lid 210 similar to FIG. 4A) above, but zoomed to a narrow range of specific electrical conductance, σ, of the lid material around the maximum temperature peak depicted on FIG. 4A) above. Furthermore, the graph also includes simulated temperature curves for four different relative permittivities, er, of the lid material ranging from 1 .5 to 12 as indicated by the curve line type on the graph. It is evident that all temperature curves exhibit a temperature peak within a relatively narrow range of specific electrical conductance from σ = 0.07 to about 0.12 Sm"1 despite the varying maximum tempera- tures. It is also evident that for the present lid design, the optimum value for er is either about 3 or about 12 even though the entire range from 1 .5 to 12 provides a pronounced and useful temperature increase of the lid.
FIG. 5) is a side perspective view of an experimental lid structure, suitable for a large-sized pharmaceutical drug capsule, with dimensions added. The dimensions of the split-ring resonator are: r ill in ! * i n: in I w !mm| g [mm] t [mm]
SA 03 03 02 L5 Accordingly, the maximum dimension (a diameter between outer edges of the outer ring 206) of the split-ring resonator can be computed from the depicted geometry as: 2* (r + 2*w + s) = 12 mm. However, the above-listed dimensions were primarily chosen for fabrication convenience in connection with experimental measurements of orientation effects on the experimental split-ring resonator. Accordingly, practical dimensions may be considerably smaller in numerous applications of the present ingestible capsule.
FIG. 6A) is schematic top view of a first alternative electrical resonance structure 600 attached to the first wall portion of the ingestible drug capsule discussed above. The resonator 600 is formed as a substantially flat and circular metallic structure 608 with a pair of radially projecting legs placed opposite to each other. The radially pro- jecting arms face each other across a gap 609 formed between facing straight edges of the legs. The lossy dielectric material of the first wall portion is arranged in, or adjacent (e.g. below), the first wall portion such that the entire continuous gap 609 is heated leading to a more evenly distributed heating of the first wall portion compared to the localized heating at the gaps of the earlier discussed split-ring resona- tor as depicted on FIG. 3B.
FIG. 6B) is schematic top view of a second alternative electrical resonance structure 650 for application as electrical resonance structure on the first wall portion of the ingestible drug capsule discussed above. The resonator 650 is formed as a substan- tially flat and continuous metallic spiral structure 658 with mating continuous gap
609 formed between facing edges of individual revolutions or arms of the spiral. The alternating electrical field is induced between facing segments of the revolutions across and along the continuous gap 659. The lossy dielectric material of the first wall portion is arranged in, or adjacent (e.g. below), the first wall portion such that the entire continuous gap 659 becomes heated leading to a more evenly distributed heating of the first wall portion compared to the localized heating at the gaps of the earlier discussed split-ring resonator as depicted on FIG. 3B.