WO2014053352A1 - Capsule pouvant être ingérée pour libération contrôlée à distance d'une substance - Google Patents

Capsule pouvant être ingérée pour libération contrôlée à distance d'une substance Download PDF

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Publication number
WO2014053352A1
WO2014053352A1 PCT/EP2013/069788 EP2013069788W WO2014053352A1 WO 2014053352 A1 WO2014053352 A1 WO 2014053352A1 EP 2013069788 W EP2013069788 W EP 2013069788W WO 2014053352 A1 WO2014053352 A1 WO 2014053352A1
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Prior art keywords
ingestible capsule
wall portion
capsule according
capsule
ingestible
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PCT/EP2013/069788
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English (en)
Inventor
Sævar Þór JÓNASSON
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Danmarks Tekniske Universitet
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Publication of WO2014053352A1 publication Critical patent/WO2014053352A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01P—WAVEGUIDES; RESONATORS, LINES, OR OTHER DEVICES OF THE WAVEGUIDE TYPE
    • H01P7/00—Resonators of the waveguide type
    • H01P7/08—Strip line resonators

Definitions

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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:
  • 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
  • '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 ⁇ ).
  • 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 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 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 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.
  • 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.
  • 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.
  • the predetermined segment may comprise smaller or larger area of the first wall portion.
  • 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.
  • the term 'lossy dielectric material' refers to a material with a specific electrical conductance, ⁇ , 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 .
  • the lossy dielectric material possesses in addition a relative permittivity, e r , between 1 .0 and 80 such as between 2.0 and 15, at the frequency of operation.
  • 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.
  • a conductive powder such as a metallic powder
  • 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.
  • 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.
  • 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.
  • 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 ' ⁇ , or even more preferably less than 3 °C.
  • the temperature increase leads to a change of the chemical or mechanical state or property of the segment itself.
  • 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.
  • the temperature in- crease in the predetermined segment of the first wall portion is conveyed by thermal coupling to a separate release mechanism.
  • 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.
  • 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 ⁇ ⁇ for example around 40 °C.
  • 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 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.
  • 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).
  • 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.
  • 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 ⁇ /10 ( ⁇ 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 ⁇ /2.
  • the small electrical size of split-ring resonators makes these highly advantageous as receiving antennas in the present ingestible drug capsule compared to ⁇ /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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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:
  • the excitation frequency of the microwave electromagnetic radiation is preferably larger than 100 MHz for the reasons discussed above.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • the constructive interference pattern of the microwave antenna structure can be adjusted.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ⁇ /10 in comparison to typical microwave resonance structures or antennas that resonate at the electrical size of ⁇ /2.
  • split-ring resonators makes these highly advantageous for application in remote drug capsule activation compared to ⁇ /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.
  • 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.
  • 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, ⁇ , 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.
  • 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.
  • the temperature sensitive polymer changes its adhesion within a temperature span less than 3 degree ' ⁇ starting with strong adhesion below a temperature of 37 ⁇ ⁇ .
  • the release mechanism comprises a lid, or other capsule wall structure, with a temperature dependent porosity.
  • the lid exhibits a porosity capable of withholding the pharmaceutical substance at a temperature at and below 37 ⁇ ⁇ , but unable to do so at a higher temperature such as 40 ' ⁇ .
  • the porosity of the porous lid material increases markedly above 40 °C and the pharmaceutical substance is released from the capsule.
  • 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 , ⁇ , of the lid base material for two different relative permittivities, e r , 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.
  • 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, e r , and relative specific electrical conduct- ance, ⁇ , 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.
  • 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.
  • 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 * 10 7 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. 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
  • 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
  • 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.

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Abstract

L'invention concerne une capsule pouvant être ingérée (102) pour administrer une substance, par exemple un médicament pharmaceutique, à un être humain ou à un animal. La capsule pouvant être ingérée comprend une structure de paroi de capsule (202) formant un réservoir ou une lumière sensiblement hermétique renfermant la substance (204). Une structure de résonance électrique, sensible à un rayonnement électromagnétique micro-onde, est fixée à une première partie de paroi de la structure de paroi de capsule qui comprend une matière diélectrique à pertes. Au moins un segment prédéterminé de la première partie de paroi est chauffé par le rayonnement électromagnétique micro-onde reçu pour déclencher un mécanisme de libération de la capsule pouvant être ingérée.
PCT/EP2013/069788 2012-10-03 2013-09-24 Capsule pouvant être ingérée pour libération contrôlée à distance d'une substance WO2014053352A1 (fr)

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EP12187095 2012-10-03
EP12187095.0 2012-10-03

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111499253A (zh) * 2020-04-15 2020-08-07 东南大学 一种基于微波控释的外加剂微胶囊及其制备方法

Citations (6)

* Cited by examiner, † Cited by third party
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