Ingestible capsule

Abstract

The present disclosure relates to an ingestible capsule (11) configured for ingestion into a lumen (6) of a patient, the ingestible capsule (11) comprising: - a capsule housing (12) with an interior (14), - a medicament (8) located inside the interior (14) of the capsule housing (12), - a tissue attachment mechanism (40) transferable from an inactive state into an active state in response to a detection of a first in vivo condition inside the lumen of the patient, wherein when in the active state the tissue attachment mechanism (40) is configured to attach the ingestible capsule (11) to biological tissue (5) adjoining or enclosing the lumen (6), - a medicament delivery mechanism (50) transferable from an idle state into a delivery state in response to a detection of a second in vivo condition inside the lumen (6) of the patient, wherein when in the delivery state, the medicament delivery mechanism (50) is configured to deliver the medicament (8) into at least one of the lumen (6) and the biological tissue (5).

Description

[0001] Ingestible Capsule

[0002] Description

[0003] Field

[0004] The present disclosure relates to the field of ingestible capsules for administering or depositing a medicament into a lumen of a patient.

[0005] Background

[0006] Ingestible capsules or pills for introduction into a bodily lumen are as such known in the art. They may serve to provide drug release and / or diagnosis of a selected lumen or tissue, e.g. in the gastrointestinal tract in the human or animal body. Ingestible capsules or respective swallowable electronic devices typically comprise a housing made from a bio-compatible material that may house electronic components in order to analyze the direct environment of the ingestible capsule, to collect or to acquire physiological parameters and / or to release or to inject a drug or medicament.

[0007] It is generally desirable to provide a well-defined dosage of a medicament that fits the patient's needs and which provides a best matching with the current physiological constitution of a patient. Typically and once ingested ingestible capsules or pills may be no longer controlled from outside the human or animal body.

[0008] It is therefore desirable to improve the functionality of ingestible capsule or pills in terms of medicament release inside a lumen of a human or animal body. Specifically, it is desirable to provide a good and / or improved release of the medicament that matches or corresponds with a momentary physiological constitution of the patient.

[0009] Summary

[0010] In one aspect there is provided an ingestible capsule, which is configured for ingestion into a lumen of a patient. The ingestible capsule comprises a capsule housing defining or comprising an interior. The ingestible capsule further comprises a medicament located inside the interior of the capsule housing. The ingestible capsule further comprises a tissue attachment mechanism, which is transferable from an inactive state into an active state in response to a detection of a first in vivo condition inside the lumen of the patient. When in the active state, the tissue attachment mechanism is configured to attach the ingestible capsule to biological tissue, which biological tissue adjoins or encloses the lumen.

[0011] The ingestible capsule further comprises a medicament delivery mechanism, which is transferable from an idle state into a delivery state in response to a detection of a second in vivo condition inside the lumen of the patient. When in the delivery state, the medicament delivery mechanism is configured to deliver the medicament into at least one of the lumen and the biological tissue. New paragraph in some examples the ingestible capsule is swallowable by a patient. The ingestible capsule is configured and intended to be moved through the gastrointestinal tract of the patient.

[0012] The ingestible capsule is further configured to detect the first in vivo condition and to detect the second in vivo condition, which may differ from the first in vivo condition. In this way different in vivo conditions can be used to trigger activation of the tissue attachment mechanism and activation of the medicament delivery mechanism, respectively. When activated the tissue attachment mechanism transfers from an inactive state into the active state. When activated the medicament delivery mechanism transfers from the idle state into the delivery state.

[0013] In this way, the detection of the first in vivo conditions and detection of the second in vivo condition can be used to trigger activation of the tissue attachment mechanism and activation of the medicament delivery mechanism, respectively.

[0014] In some examples the tissue attachment mechanism is particularly configured to attach and / or to anchor the ingestible capsule to a particular region of the gastrointestinal tract of the patient. When activated or upon activation of the tissue attachment mechanism the ingestible capsule can be fixed or anchored to a selected region of the gastrointestinal tract, which may be characterized by the first in vivo condition. When activated the tissue attachment mechanism serves to fix the ingestible capsule to the selected region of the lumen of the patient, in which the first in vivo condition is fulfilled.

[0015] In some examples activation of the medicament delivery mechanism requires a preceding activation of the tissue attachment mechanism. In other words, the ingestible capsule is configured to activate the medicament delivery mechanism only and / or exclusively after activation of the tissue attachment mechanism. In this way it can be guaranteed that the medicament is delivered or released into the lumen or biological tissue that fulfills both, the first in vivo condition and the second in vivo condition.

[0016] In some examples, in which after ingestion or swallowing of the ingestible capsule only the first in vivo condition will be detected or fulfilled the medicament delivery mechanism may remain inactive and the ingestible capsule may leave the gastrointestinal tract without delivery or release of a medicament.

[0017] In other examples and wherein after swallowing or ingestion of the ingestible capsule the first in vivo condition will not be detected the tissue attachment mechanism may remain inactive and the ingestible capsule may leave the gastrointestinal tract rather rapidly. In some examples the medicament delivery mechanism may be exclusively transferable from the idle state into the delivery state when both of the following conditions are met: i) activation of the tissue attachment mechanism and ii) detection of the second in vivo condition. In this way it can be guaranteed that the medicament is only delivered or released into the lumen when the tissue attachment mechanism has been activated and transferred into the active state. In this way an uncontrolled delivery or release of the medicament into a portion of the lumen or biological tissue, where the first in vivo condition would not be met or fulfilled can be effectively prevented.

[0018] According to a further example the ingestible capsule comprises a detector arrangement, which is configured to detect at least one of the first in vivo condition and the second in vivo condition inside the lumen of the patient. By way of the detector arrangement different physiological parameters can be qualitatively and / or quantitatively detected or even measured. By way of the detector arrangement the in vivo conditions can be precisely detected and at least one or both of the tissue attachment mechanism and the medicament delivery mechanism can be triggered as soon as the respective in vivo condition is met.

[0019] In some examples the detector arrangement is configured to detect the first in vivo condition and the second in vivo condition. In further examples the detector arrangement is configured to distinguish between the first in vivo condition and the second in vivo condition.

[0020] In some examples the detector arrangement is provided as a separate unit. It may be located on or inside the capsule housing. It may form part of the capsule housing so as to precisely detect the first and the second in vivo conditions in the vicinity of the ingestible capsule outside the ingestible capsule.

[0021] In some examples the detector arrangement may be operatively coupled with at least one of the tissue attachment mechanism and the medicament delivery mechanism. In some examples and when the detector arrangement is configured to detect both, the first in vivo condition and the second in vivo condition the detector arrangement may be operatively coupled to the tissue attachment mechanism and to the medicament delivery mechanism. In this way, the detector arrangement may serve to trigger transferring of the tissue attachment mechanism from the inactive state into the active state and may be operable to trigger transferring of the medicament delivery mechanism from the idle state into the delivery state.

[0022] In some examples the detector arrangement may be integrated or may form part of at least one of the tissue attachment mechanism and the medicament delivery mechanism. Insofar, there may be provided a first detector arrangement and a second detector arrangement. The first detector arrangement may be integrated into the tissue attachment mechanism and the second detector arrangement may be integrated or associated with the medicament delivery mechanism. Here, first and second detector arrangements may be configured or dedicated to detect only one of the first in vivo condition and the second in vivo condition. In some examples the first detector arrangement may be configured to detect the first in vivo condition and the second detector arrangement may be configured to detect the second in vivo condition. Upon detection of the respective in vivo conditions the detector arrangement may be then configured to trigger activation of the tissue attachment mechanism and / or of the medicament delivery mechanism, to which the respective detector arrangement is operatively coupled.

[0023] According to a further example the ingestible capsule further comprises a controller, which is coupled to at least one of the tissue attachment mechanism and the medicament delivery mechanism. The controller is configured to trigger activation of at least one of the tissue attachment mechanism and the medicament delivery mechanism. Upon activation of the tissue attachment mechanism the tissue attachment mechanism transfers from the inactive state into the active state. Upon activation of the medicament delivery mechanism the medicament delivery mechanism transfers from the idle state into the delivery state. The controller may comprise an electronic circuit and / or a logic circuit by way of which at least one of the tissue attachment mechanism and the medicament delivery mechanism can be actuated.

[0024] The controller may provide an electric or electronic signal processing, which signals might be indicative of the detection of at least one of the first in vivo condition and the second in vivo condition. The controller may be configured to trigger activation of the tissue attachment mechanism when receiving a signal being indicative of the detection of the first in vivo condition. The controller may be further configured to trigger activation of the medicament delivery mechanism when processing or receiving a signal being indicative of a detection of the second in vivo condition. According to another example the controller is coupled to the detector arrangement. The controller is operable to trigger activation of at least one of the tissue attachment mechanism and the medicament delivery mechanism in response to the detector arrangement detecting at least one of the first in vivo condition and the second in vivo condition.

[0025] In some examples the detector arrangement may be configured to generate processable signals, which are processable by the controller. In some examples the detector arrangement may be configured to generate a first electrical signal being indicative of a detection of the first in vivo condition. The detector arrangement may be further configured to generate a second electrical signal being indicative of a detection of the second in vivo condition. Insofar, the processor coupled or connected to the detector arrangement may be operable to provide signal processing, e.g. processing of electrical signals obtained or obtainable from the detector arrangement, which electrical signals are indicative of the detection of at least one of the first in vivo condition and the second in vivo condition. In some examples the processor may be configured for digital signal processing.

[0026] According to a further example of the ingestible capsule the first in vivo condition is one of a first predetermined temperature, a first predetermined pH value, a first predetermined enzymatic environment and a first predetermined electrical conductivity. Hence, the detector arrangement may be configured to detect at least one of a temperature, a pH value, an enzymatic environment and an electrical conductivity in the vicinity of the ingestible capsule. In this way, at least one of a predetermined temperature, a predetermined pH value, a predetermined enzymatic environment and a first electrical conductivity can be used to trigger activation of the tissue attachment mechanism.

[0027] According to a further example the second in vivo condition is one of a second predetermined temperature, a second predetermined pH value, a second predetermined enzymatic environment and a second electrical conductivity. The second predetermined temperature distinguishes from the first predetermined temperature. The second predetermined pH value distinguishes from the first predetermined pH value. The second predetermined enzymatic environment distinguishes from the first predetermined enzymatic environment and the second predetermined electrical conductivity distinguishes from the first predetermined electrical conductivity.

[0028] In some examples the first in vivo condition and the second in vivo condition may be characterized by the same physiological parameter. Here, the first in vivo condition may be a first predetermined temperature and the second in vivo condition may be a second predetermined temperature. Here, the tissue attachment mechanism may be activated upon detection of a first predetermined temperature inside the lumen of the patient. The ingestible capsule, specifically its medicament delivery mechanism may then remain inactive as long as the second predetermined temperature has not been detected or reached. It may be only upon a change, e.g. a rise or decrease temperature in the lumen of the patient, that the second in vivo condition is met or detected.

[0029] Insofar, the ingestible capsule can be ingested or swallowed precautiously, hence as a precautionary measure. It may be then upon detection of a first predetermined temperature that the tissue attachment mechanism is activated, which provides a fastening or anchoring of the ingestible capsule in the lumen or in a specific portion of the lumen, e.g in the gastrointestinal tract of the patient. Then, the ingestible capsule is configured to wait until the second predetermined temperature inside the lumen is reached. It may be only upon detection of the second predetermined temperature, which may be higher or lower than the first predetermined temperature that the medicament delivery mechanism is activated, which then leads to the release or delivery of the medicament into biological tissue or into the lumen of the patient.

[0030] Likewise, the same mechanism and mode of operation may be also implemented in view of any other of the above mentioned physiological or physical parameters: pH value, enzymatic environment or electrical conductivity.

[0031] In some examples the first and the second in vivo conditions may be of different type. For example, when the first in vivo condition is a first predetermined temperature the second in vivo condition is one of the second predetermined pH value, the second predetermined enzymatic environment at the second electrical conductivity. When the first in vivo condition is e.g. a first predetermined pH value, the second in vivo condition is one of a second predetermined temperature, a second predetermined enzymatic environment and a second predetermined electrical conductivity.

[0032] In some examples and when the first in vivo condition is a first predetermined enzymatic environment, the second in vivo condition is one of a second predetermined temperature, a second predetermined pH value and a second predetermined electrical conductivity. In further examples and when the first in vivo condition is a first predetermined electrical conductivity, the second in vivo condition is one of the second predetermined temperature, a second predetermined pH value and a second predetermined enzymatic environment. In this way, different physiological parameters can be used to trigger the tissue attachment mechanism and the medicament delivery mechanism, respectively.

[0033] The specific selection or implementation of first and second in vivo conditions may depend on the type of medicament and the type of therapy for which the ingestible capsule is intended or configured for.

[0034] According to a further example the sensor arrangement is configured to quantitatively measure at least one physiological parameter or physical parameter being indicative of or being related to at least one of the first and in vivo condition and the second in vivo condition. Such physiological parameters or physical parameters may be one of the first or second predetermined temperature, one of the first and second predetermined pH value, one of the first and second predetermined enzymatic environment and one of the first or second predetermined electrical conductivity.

[0035] A quantitative measuring of at least one of the above-mentioned physiological parameters may provide a rather precise activation of the tissue attachment mechanism and / or activation of the medicament delivery mechanism. A quantitative measurement of at least one of the above- mentioned physiological parameters or physical parameters may be further beneficial to modify or to control at least one of the activation of the tissue attachment mechanism and activation of the medicament delivery mechanism.

[0036] According to a further example the tissue attachment mechanism is transferable from the active state into the inactive state or into an inoperable state upon lapse of a predefined time interval since it has been activated and / or upon detection of a third in vivo condition inside the lumen of the patient. In this way a controlled disconnection or detachment of the tissue or attachment mechanism from the biological tissue, to which it has provided an attachment of the ingestible capsule, can be provided.

[0037] Transferring of the tissue attachment mechanism into the inactive or inoperable state provides an effective means to release and / or to detach the ingestible capsule from the biological tissue and to allow a further transportation of the ingestible capsule through the gastrointestinal tract until it leaves the lumen of the patient. The transfer of the tissue attachment mechanism from the active state into the inactive or inoperable state provides an effective means to terminate operation and / or medicament delivery of the ingestible capsule. The ingestible capsule may leave the lumen of the patient undigested. Detection or measuring of a third in vivo condition may be provided by the tissue attachment mechanism itself. In some examples the detection of the third in vivo condition may be provided by the detector arrangement, which may then trigger deactivation of the tissue attachment mechanism, e.g., via the controller.

[0038] The third in vivo condition may be one of a third predetermined temperature, a third predetermined pH value, a third predetermined enzymatic environment and a third electrical conductivity. In some examples and for instance when the first, the second and the third in vivo condition may be a first predetermined temperature, a second predetermined temperature and a third predetermined temperature, respectively, it can be provided that the ingestible capsule is anchored or fastened to a selected portion of the lumen of the patient when detecting a first temperature.

[0039] A rise or drop of the temperature inside the lumen of the patient may then trigger or activate the medicament delivery mechanism. Thereafter and when detecting a further variation of the temperature, and hence when detected the third predetermined temperature, which may distinguish from at least one of the first predetermined temperature and the second predetermined temperature, the tissue attachment mechanism may be deactivated and may transfer into the inactive state or into an inoperable state thus leading to a further transportation of the ingestible capsule through the lumen or gastrointestinal tract of the patient.

[0040] In other examples and when the tissue attachment mechanism may be transferred into the inoperable state it may not be activated again. When and once in the inoperable state the tissue attachment mechanism cannot be activated again. In other examples and once the tissue attachment mechanism has been activated and has transferred from the inactive state into the active state it may only and exclusively transfer into the inoperable state, in which the tissue attachment mechanism is and remains substantially inoperable. This way, a repeated or unintended activation of the tissue attachment mechanism can be effectively prevented.

[0041] According to a further example the tissue attachment mechanism comprises at least one tissue attachment element, which is configured for fastening to the biological tissue. The tissue attachment element is at least one of the deployable or movable relative to the capsule housing into at least one of an expanded or extended configurations upon transferring the tissue attachment mechanism from the inactive state into the active state. The tissue attachment element may be movable relative to the capsule housing.

[0042] In the active state or active configuration of the tissue attachment mechanism the tissue attachment element may protrude from an outside of the capsule housing. The tissue attachment element may then provide attachment to the biological tissue. The tissue attachment element may comprise a kind of an anchoring element or piercing element that is configured to anchor or to pierce into the biological tissue thereby serving to fix and / or to attach the tissue attachment element to the biological tissue, thereby fixing or fastening the ingestible capsule to the biological tissue, e.g. to a sidewall or wall of the lumen of the patient.

[0043] In other examples the tissue attachment element may be deployable into an extended or expanded configuration, in which the tissue attachment element, e.g. readily protruding from an outside of the capsule housing transfers into an expanded or extended configuration, in which it may provide a likewise attaching or fastening to biological tissue.

[0044] In some examples the tissue attachment element may increase its dimensions upon activation of the tissue attachment mechanism thereby providing an effective attachment for adhering to a wall of the lumen or to tissue enclosing or adjoining the lumen of the patient.

[0045] According to a further example the tissue attachment element may be separable or detachable from the tissue attachment mechanism upon detection of the third in vivo condition inside the lumen of the patient. Here, the tissue attachment element may remain fastened or anchored in the biological tissue after its activation. A transfer of the tissue attachment mechanism from the active state into the inactive state may then include a detachment of the tissue attachment element from the ingestible capsule.

[0046] The separation of the tissue attachment element, which may remain fastened to the biological tissue, from the ingestible capsule may release the ingestible capsule from the biological tissue, to which the tissue attachment element may remain fastened or fixed. In this example the tissue attachment element may comprise or may be made of a biocompatible material. It may be digestible and may dissolve in the gastrointestinal tract after a while.

[0047] In this way and even when a third in vivo condition could not be actively detected a biocompatible and / or digestible or dissolvable tissue attachment element may automatically provide a detachment of the ingestible capsule from the biological tissue and a complete transportation of the ingestible capsule through the gastrointestinal tract.

[0048] According to a further example the tissue attachment element is biodegradable. According to a further example the tissue attachment mechanism comprises an actuator for moving of the tissue attachment element or for deploying the tissue attachment element. By way of the actuator, which may be driven by a source of energy, e.g. by a pressure source or by an electric energy source there can be provided a rather controlled and defined movement or deploying of the tissue attachment element. The actuator may provide a movement or deploying, e.g. extension or expansion of the tissue attachment element and may transfer a respective stored energy into a movement or expansion of the tissue attachment element.

[0049] According to a further example actuation of the actuator is controlled by the controller. In this way, transfer of energy from a source of energy to the actuator may be controlled by the controller. Moreover, the controller may be also configured to control the process of moving or deploying the tissue attachment element. In this way, the controller may provide a precise control and / or operation of the tissue attachment mechanism.

[0050] According to another example the medicament delivery mechanism comprises a medicament reservoir provided with the medicament and a delivery unit. The delivery unit is connected to the medicament reservoir in a medicament transferring manner. The medicament reservoir may be configured to store or to provide a medicament in liquid form, in powder form or as a granular material. When the medicament is stored in the medicament reservoir in a liquid form the delivery mechanism may be configured to expel the medicament into the lumen or into the biological tissue by way of injection.

[0051] The delivery unit may be particularly configured to deliver or to release the medicament stored in the medicament reservoir. Hence, upon activation of the medicament delivery mechanism the medicament stored or provided by the medicament reservoir can be transferred to the delivery unit through which the medicament may be released, e.g. expelled or injected into one of the lumen and the biological tissue in the vicinity of the ingestible capsule.

[0052] According to a further example the delivery unit comprises a drive mechanism and a delivery element connected to the medicament reservoir. The delivery element may belong to the delivery unit. The drive mechanism may be operable to interact with at least one of the medicament reservoir, the delivery unit and the delivery element. The drive mechanism is particularly configured to expel the medicament from the medicament reservoir through the delivery element into at least one of the lumen or biological tissue in direct vicinity of the ingestible capsule.

[0053] The drive mechanism may be particularly configured to expel or to withdraw a dose of the medicament from the medicament reservoir. The drive mechanism may be also configured to withdraw or to expel the entirety of the medicament located inside the medicament reservoir through the delivery element into biological tissue or into the lumen in direct vicinity of the ingestible capsule. The drive mechanism may be provided with a source of energy, e.g. a mechanical source of energy, such as a spring. In some examples the drive mechanism may be provided with an electrical source of energy. Then, the drive mechanism may be further provided with an electromechanical actuator, which serves to transfer electrical energy stored in the electrical source of energy into an expelling or withdrawing motion of the medicament from the medicament reservoir.

[0054] According to a further example the delivery unit comprises a tissue penetrating element, which is configured to penetrate or to pierce the biological tissue for medicament delivery into the biological tissue. The tissue penetrating element may comprise a tipped cannula or needle, through which a liquid medicament may be delivered or injected into the biological tissue in direct vicinity of the ingestible capsule.

[0055] In some examples and when the medicament delivery mechanism is activated the drive mechanism of the delivery unit may be configured to move at least one of the delivery unit, the delivery element and the tissue penetrating element into an activated state or activated configuration, in which the respective component, i.e. the delivery unit, the delivery element and / or the tissue penetrating element protrudes from the outside of the capsule housing. In this way, there can be provided an effective piercing of the biological tissue in direct vicinity of the ingestible capsule.

[0056] According to a further example the medicament delivery mechanism is transferable from the delivery state into at least one of the idle state and an inoperable state in response to a detection of a fourth in vivo condition inside the lumen of the patient. When in one of the idle state and the inoperable state the medicament delivery mechanism is inoperable to deliver the medicament into one of the lumen and the biological tissue.

[0057] Here and when the medicament delivery mechanism is transferred from the delivery state into the idle state it may be activated again and may transfer back from the idle state to the delivery state, e.g. when the second in vivo condition is met or detected. In other examples and when the medicament delivery mechanism is exclusively transferable from the delivery state into the operable state a re-activation, i.e. a re-transfer the inoperable state into the delivery state or active state is no longer possible. Here, the medicament delivery mechanism may be implemented as a kind of a disposable or single use medicament delivery mechanism. If the medicament delivery mechanism is transferable from the idle state into the delivery state and back into the idle state, the medicament delivery mechanism may be activated multiple times depending on the detection of the second and fourth vivo conditions. When detecting the second in vivo condition the medicament delivery mechanism may be transferred from the idle state into the delivery state. Upon detection of the fourth in vivo condition the medicament delivery mechanism is transferable from the delivery stage back into the idle state. This allows and support a multiple activation and deactivation of the medicament delivery mechanism, by way of which medicament therapy may be optimized.

[0058] According to a further example the fourth in vivo condition is one of a fourth predetermined temperature, a fourth predetermined pH value, a fourth predetermined enzymatic environment and a fourth electrical conductivity. Here, the predetermined fourth temperature may distinguish from at least one of the first, the second and the third predetermined temperatures. Likewise, the fourth predetermined pH value may distinguish from at least one of the first, the second and the third predetermined pH values. The fourth predetermined enzymatic environment may distinguish from at least one of the first, the second and the third engine environments and the fourth electrical conductivity may distinguish from at least one of the first, the second and the third predetermined electrical conductivities.

[0059] Specifically, the fourth predetermined temperature, the fourth predetermined pH value, the fourth predetermined enzymatic environment and the fourth predetermined electrical conductivity may distinguish from the respective second predetermined temperature, second predetermined pH value, second predetermined enzymatic environment and the second predetermined electrical conductivity.

[0060] A modification of at least one of the above-mentioned physiological or physical parameters over time, e.g. during which the ingestible capsule is attached of fixed to the biological tissue, e.g. via the activated tissue attachment mechanism, may be due to the release or delivery of the medicament. This may then trigger a deactivation of the medicament delivery mechanism.

[0061] According to a further example detecting and / or quantitatively measuring of at least one of the first in vivo condition, the second in vivo condition, the third in vivo condition and the fourth in vivo condition may be continued on may take place even during medicament delivery of a medicament release while the medicament delivery mechanism is in the delivery state. The continuous or stepwise monitoring, detecting or quantitative measuring of at least one physiological or physical parameter, which may be subject to modifications due to the delivery or release of the medicament may allow to reduce or to interrupt medicament delivery before a content of a medicament reservoir provided inside the interior of the capsule is empty. In this way, the medicament can be rather effectively used. Avoiding of an overdosing of the medicament can be actively controlled.

[0062] Accordingly, the ingestible capsule as a described herein may be effective to provide or to establish a control loop by way of which a physiological or physical parameter in the environment of the ingestible capsule matches a predefined value or parameter range. In this way, a selected region of the gastrointestinal tract can be suitably prepared for further medicament administration, which for the medicament administration may require a particular temperature or pH value or enzymatic environmental conditions to unfold its therapeutic effect optimally.

[0063] According to another aspect the present disclosure also relates to a method of controlling operation of an ingestible capsule as described above. The method comprises the steps of detecting of the first in vivo condition inside the lumen of the patient, transferring the tissue attachment mechanism of the ingestible capsule from an inactive state into an active state in response to the detection of the first in vivo condition, detecting of a second in vivo condition inside the lumen of the patient and enabling a transferring of the medicament delivery mechanism from an idle state into a delivery state in response to the detection of the second in vivo condition.

[0064] In some examples the method of controlling operation terminates with the detection of the second in vivo condition inside the lumen of the patient and the enabling of transferring of the medicament delivery mechanism from the idle state into the delivery date in response to the detection of the second in vivo condition.

[0065] In some examples of the method and since the method is configured to control operation of an ingestible capsule as described above, all features, effects and benefits as described above in connection with the ingestible capsule may equally apply to the method of controlling operation of the ingestible capsule; and vice versa.

[0066] In a further example of the method, detecting of the second in vivo condition is impeded or blocked until the first in vivo condition has been detected and / or until the tissue attachment mechanism has been transferred into the active state. In this way, a premature activation of the medicament delivery mechanism can be effectively blocked or impeded and a respective medicament delivery can be prevented. In this way, delivery or release of the medicament into biological tissue without a preceding activation of the tissue attachment mechanism can be effectively prevented. Hence, an uncontrolled release or delivery of the medicament into biological tissue, wherein the first in vivo condition is not met, can be effectively prevented and patient safety can be increased.

[0067] According to a further example an enabling of the transferring of the medicament delivery mechanism from the idle state into the delivery state is blocked or impeded until the first in vivo condition has been detected, until the second in vivo condition has been detected and until the tissue attachment mechanism has been transferred into the active state. In this way, the medicament delivery mechanism is only then enabled to release or to transfer into the delivery state if all three prerequisites are met, namely: detection of first and second in vivo conditions as well as a preceding activation of the tissue attachment mechanism. In this way it can be guaranteed that a subsequent medicament delivery can only take place when the respective in vivo conditions are met or detected and when the ingestible capsule has been attached to the lumen or biological tissue of the patient.

[0068] Generally, the scope of the present disclosure is defined by the content of the claims. The disclosure is not limited to specific embodiments or examples but comprises any combination of elements of different embodiments or examples. Insofar, the present disclosure covers any combination of claims and any technically feasible combination of the features disclosed in connection with different examples or embodiments.

[0069] In the present context the term ‘distal’ or ‘distal end’ relates to an end of the injection device that faces towards an injection site of a person or of an animal. The term ‘proximal’ or ‘proximal end’ relates to an opposite end of the injection device, which is furthest away from an injection site of a person or of an animal.

[0070] The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0071] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0072] The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., shorter long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dualchamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

[0073] The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.

[0074] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.

[0075] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0076] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.

[0077] Examples of GLP-1 , GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP-1 Eligen, GRMD-0901 , NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1 , CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701 , MAR709, ZP- 2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA- 15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide- XTEN and Glucagon-Xten.

[0078] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom. Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0079] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0080] Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0081] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV). The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0082] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0083] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

[0084] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

[0085] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

[0086] An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needle- based injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0087] As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

[0088] As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

[0089] Brief description of the drawings

[0090] In the following, examples of ingestible capsules as described herein are illustrated in greater detail by making reference to the drawings, in which:

[0091] Fig. 1 is a schematic block diagram of an ingestible capsules in an initial configuration,

[0092] Fig. 2 shows the ingestible capsule after a first activation step,

[0093] Fig. 3 shows the ingestible capsule after or during a second activation step,

[0094] Fig. 4 shows the ingestible capsule after completion of medicament delivery, and

[0095] Fig. 5 shows a flowchart of a method of operating an ingestible capsule.

[0096] Detailed description

[0097] In Fig. 1 there is shown one example of an ingestible capsule 11 , which forms or constitutes a drug delivery device 10 for ingestion or swallowing by a patient. The drug delivery device 10 and hence the ingestible capsule 11 comprises a capsule housing 12. The capsule housing 12 defines or comprises an interior 14, in which numerous components of the ingestible capsule 11 are arranged. Inside the interior 14 there is provided a medicament reservoir 51 containing a medicament 8. The ingestible capsule 11 further comprises a tissue attachment mechanism 40 and a medicament delivery mechanism 50. The tissue attachment mechanism 40 is transferable from an inactive state as e.g. shown in Fig. 1 into an active state in response to a detection of a first in vivo condition inside a lumen 6 of a patient.

[0098] The lumen 6 may adjoin to or may be confined by biological tissue 5 of the patient. The lumen 6 may be located inside the gastrointestinal tract of the patient. Numerous sections of the gastrointestinal tract, such as the stomach, the small intestine, the large intestine or the duodendum and further sections of the gastrointestinal tract may provide different and distinguishable in vivo conditions. By detecting a first in vivo condition, e.g. inside the small intestine the tissue attachment mechanism may be transferred from the inactive state into the active state. By activating the tissue attachment mechanism 40 the tissue attachment mechanism 40 may deploy or may be configured to move tissue attachment elements 41 as shown in Fig. 2 into an activated position or activated configuration. The tissue attachment mechanism 40 may comprise an actuator 42 for moving of the tissue attachment element 41 or for deploying the tissue attachment elements 41.

[0099] By way of example the tissue attachment element or numerous tissue attachment elements 41 may protrude from the outside of the capsule housing 12. The individual tissue attachment elements 41 may comprise one of a microneedle or some comparable piercing or anchoring elements, which may penetrate or pierce a portion of the biological tissue 5, which surrounds, encloses or adjoins the lumen 6. By way of activating the tissue attachment mechanism 40 and / or by way of moving or deploying at least one or several tissue attachment elements 41 the ingestible capsule 11 can be attached to the biological tissue 5 as e.g. indicated in Fig. 3.

[0100] The ingestible capsule 11 further comprises a medicament delivery mechanism 50. In the illustrated example the medicament delivery mechanism 50 comprises a delivery unit 51 , which is in a medicament transferring connection or medicament transferring coupling with the medicament reservoir 51. The medicament delivery mechanism may be also transferable from the idle or inactive state into a delivery state, which transfer is apparent from a comparison of Figs. 2, 3 and 4. When in the delivery state as shown in any of the Figs. 3 or 4, the medicament delivery mechanism is operable or configured to deliver or to release the medicament 8 into at least one of the lumen 6 and the biological tissue 5. The medicament delivery mechanism may be exclusively transferable from the idle state into the delivery state in response to a detection of a second in vivo condition inside the lumen 6 of the patient and outside 16 of the ingestible capsule 11.

[0101] The ingestible capsule 11 may optionally also comprise a controller 20, which may be operably linked or coupled to at least one of the tissue attachment mechanism 40 and the medicament delivery mechanism 50. Moreover, the ingestible capsule 11 may comprise a detector arrangement 30. The detector arrangement 30 may be particularly configured to detect the first in vivo condition and the second in vivo condition, e.g., outside 16 the ingestible capsules and / or in direct vicinity of the capsule 11. In some examples the detector arrangement 30 comprises a first detector 31, e.g. for detecting the first in vivo condition. The detector arrangement 30 may further comprise a second detector 32, e.g. for detecting the second in vivo condition. In other examples, any one of the first and the second detectors 31 , 32 may be configured to detect or to measure the first in vivo condition and the second in vivo condition.

[0102] The detector arrangement 30 may be operably linked or coupled to the controller 20. Both, the detector arrangement 30 as well as the controller 20 may be implemented electrically or electronically. The individual detectors 31, 32 may comprise an electric or electronic detector or a respective electric or electronic sensor being operable to detect at least one of the first in vivo condition and the second in vivo condition. Upon detecting at least one of the first in vivo condition and the second in vivo condition the detector arrangement 30 may be operable to generate and to transmit a respective electric detection signal to the controller 20. The controller 20 may be then operable to process the detection signal in order to trigger activation of at least one of the tissue attachment mechanism 40 and the medicament delivery mechanism 50.

[0103] The first in vivo condition may be one of a first predetermined temperature, a first predetermined pH value, a first predetermined enzymatic environment and a first predetermined electrical conductivity. Detection of a respective first parameter, e.g., by the detector arrangement 30 may trigger activation of the tissue attachment mechanism. In response to the detection of the first in vivo condition the tissue attachment mechanism 40 may be operable to move or to deploy the tissue attachment elements 41 as shown in Fig. 2. As a consequence, and with the deployed or expanded or extended tissue attachment elements 41, e.g. protruding from an outside of the capsule housing 12 the ingestible capsule 11 may attached, fix or adhere to biological tissue 5 that encloses, confines or adjoins the lumen 6.

[0104] With the activated tissue attachment mechanism 40 as shown in Fig. 3 the ingestible capsule 11 may remain inactive for a while. In this configuration, wherein only the tissue attachment mechanism has been activated and wherein the medicament delivery mechanism remains in the idle state the ingestible capsule 11 continues to remain inactive and continues to analyze or to characterize the environment and the vicinity outside the ingestible capsule 11 inside the lumen 6. In case that a second in vivo condition may be detected, e.g., by the detector arrangement 30, the controller 20 may process a respective electric detection signal and may then trigger activation of the medicament delivery mechanism 50.

[0105] The medicament delivery mechanism 50 may comprise a drive mechanism 53, by way of which a delivery unit 52 may be deployed or moved into a dispensing or drug delivery configuration as e.g. shown in Fig. 3. In some examples and upon transferring or switching the medicament delivery mechanism 50 from the idle state into the delivery state the delivery unit 52 may at least partially protrude from an outside of the capsule housing 12 as e.g. shown in Fig. 3. In other examples it may not be required that the delivery unit 52, which is in flow communication with the medicament reservoir 51 protrudes from the outside of the capsule housing 12. It may be sufficient when an exit or outlet of the delivery unit 52 flushes with the capsule housing 12.

[0106] Upon switching of the medicament delivery mechanism from the idle state into the delivery state medicament delivery or medicament release through the delivery unit 52 may take place.

[0107] In the example as shown in Fig. 3 or 4, the medicament delivery mechanism 50 may be further provided with a delivery element 54, which may also protrude from the outside of the capsule housing 12 when the medicament delivery mechanism has switched or transferred into the delivery state. The delivery element 54 may be configured to puncture or to pierce into the biological tissue 5 in order to inject the medicament into the biological tissue 5.

[0108] In some examples the delivery element 54 may comprise a tipped hollow cannula and may thus comprise or constitute a tissue penetrating element 56. Movement or deploying of the delivery unit 52 and / or of the delivery element 54 may be controlled and / or conducted by the drive mechanism 53 of the delivery unit 52.

[0109] In some examples the drive mechanism 53 may be implemented as an electromechanical drive mechanism. The drive mechanism 53 may comprise an electromechanical actuator, which is configured to transfer electrical energy, e.g. provided by an electric energy source, into a mechanical movement of at least one of the delivery unit 52 and the delivery element 54. In Fig. 5 an end of a delivery action is illustrated. After dispensing or releasing or delivery of at least a portion, e.g., of a dose of the medicament from the medicament reservoir 51, the delivery element 54 may be retracted into the delivery unit 52 and / or the delivery unit 52 may be retracted back into the capsule housing 12 (not illustrated).

[0110] Likewise or additionally, the tissue attachment mechanism may be transferred into one of an inactive state or inoperable state. In Fig. 5 an inactive state is illustrated. Here, the tissue attachment elements 41 may be transferred into an initial configuration. The tissue attachment elements 41 may be retracted back into the capsule housing 12 thereby detaching the individual tissue attachment elements 41 from the biological tissue 5. Retracting of the tissue attachment elements 41 into the capsule housing 12 leads to a detachment of the ingestible capsule 11 from the biological tissue 5. As a consequence, the ingestible capsule 11 may be then further transported further through the lumen 6 until leaving the body of the patient or animal.

[0111] In Fig. 6 an example of transferring the tissue attachment mechanism into an inoperable state is illustrated. Here, the tissue attachment elements 41 may separate from the tissue attachment mechanism 40 and / or from the ingestible capsule 11. Upon detection of a third in vivo condition, which may be one of a third predetermined temperature, a third predetermined pH value, a third predetermined enzymatic environment and a third predetermined electrical contact, the tissue attachment elements 41 separate from the ingestible capsule 11 and may remain fastened or fixed to the biological tissue 5. Here, the tissue attachment elements 41 may be biocompatible and may dissolve or disintegrate or may be otherwise digested in the gastrointestinal tract of the patient. The ingestible capsule 11 may in turn move along the gastrointestinal tract until it leaves the body of the patient.

[0112] The ingestible capsule 11 as described herein is configured to fix or to attach to a selected or predetermined portion of the gastrointestinal tract of a patient, e.g. in the small intestine. This attaching or fixing is accomplished and / or provided by the tissue attachment mechanism in response to the detection of a first in vivo condition, which may characterize the selected or predetermined portion of the gastrointestinal tract. Here, the first in vivo condition may be indicative of a particular section of the gastrointestinal tract. It may be characterized by a temperature, by a pH value, by an enzymatic environment and / or by an electrical conductivity.

[0113] Once the tissue attachment mechanism has been activated the ingestible capsule may be anchored or fixed inside the lumen of the patient. It may be and remain inactive as long as a second in vivo condition has not been detected or not been reached. In some examples the first in vivo condition is one of a first predetermined temperature, a first predetermined pH value, a first predetermined engine environment and a first predetermined electrical conductivity. Detecting of one of these physiological or physical parameters triggers activation of the tissue attachment mechanism, which in turn leads to the fastening or fixing of the ingestible capsule 11 to the tissue 5.

[0114] Thereafter, the ingestible capsule 11 may remain in a rather inactive state or idle configuration. In some examples the ingestible capsule 11 may detect a rise in temperature, e.g. as a cause of a development of fever of the patient. If the temperature reaches a raised predetermined second temperature the medicament delivery mechanism may be automatically activated and medicament delivery may start.

[0115] Delivery of the medicament may take place either into the lumen 6 or into the biological tissue 5, e.g. by way of a simple release of the medicament into the lumen 6 and / or by way of injecting the medicament into the biological tissue 5. Release or delivery of the medicament 8 into the lumen 6 or biological tissue 5 may have a respective effect on the second in vivo condition. It may cause a lowering of the body temperature. In some examples and when the fourth in vivo condition may be a fourth predetermined temperature, e.g. below the second predetermined temperature detection of the fourth predetermined temperature, e.g. by the detector arrangement 30 may trigger the activation of the medicament delivery mechanism 50.

[0116] In this way and as an immediate reaction to a change of a physiological or physical parameter detectable by the detector arrangement 30, delivery of the medicament into the tissue 5 or lumen 6 may promptly terminate. Concurrently or thereafter, a deactivation of the medicament delivery mechanism, e.g. a transfer of the medicament delivery mechanism 50 into one of the idle state or an inoperable state may also trigger a quasi - automated deactivation of the tissue attachment mechanism, which may then transfer into one of the inactive state or inoperable state.

[0117] As a consequence, and after delivery of the medicament the ingestible capsule may be promptly moved through the gastrointestinal tract and may promptly leave the lumen and / or the body of the patient or animal.

[0118] The flowchart of Fig. 7 illustrates an example method of controlling operation of the ingestible capsule 11. In a first step 100 the ingestible capsule 11 is swallowed and is hence inserted into the gastrointestinal tract of the patient. It may move through a lumen 6 of the patient. In a subsequent step 102 the ingestible capsule monitors a physiological or physical parameter associated with a first in vivo condition. If in a subsequent step 104 the first in vivo condition has not been detected the method returns to step 102. The loop of steps 102 and 140 is executed as long as in step 104 the first in vivo condition is detected. Upon detection of the first in vivo condition in step 104 the method proceeds with step 106. In step 106 the tissue attachment mechanism 40 is activated. It is transferred from an inactive state into an active state in response to the detection of the first in vivo condition inside the lumen 6 of the patient.

[0119] In a subsequent step 108 it is checked whether the second in vivo condition is met or detected. Here, the ingestible capsule monitors a further or the same physiological or physical parameter associated with the second in vivo condition. As long as the second in vivo condition is not detected in step 110 the method conduct a loop of steps 108 and 110. When returning to step 108 a further measurement or detection step is conducted. The loop of steps 108 and 110 is executed as long as in step 110 the second in vivo condition is detected. As a consequence and after detection of the second in vivo condition in step 110 the method continues with step 112 and transfers the medicament delivery mechanism 50 from the idle state into the delivery state. In a further optional step 114 the medicament delivery mechanism may start to release or to deliver a medicament into one of the lumen 6 and the biological tissue 5.

[0120] Reference Numbers

[0121] 5 tissue

[0122] 6 lumen

[0123] 8 medicament

[0124] 10 drug delivery device

[0125] 11 ingestible capsule

[0126] 12 capsule housing

[0127] 14 interior

[0128] 16 exterior

[0129] 20 controller

[0130] 30 detector arrangement

[0131] 31 detector

[0132] 32 detector

[0133] 40 tissue attachment mechanism

[0134] 41 tissue attachment element

[0135] 42 actuator

[0136] 50 medicament delivery mechanism

[0137] 51 medicament reservoir

[0138] 52 delivery unit

[0139] 53 drive mechanism

[0140] 54 delivery element

[0141] 56 tissue penetrating element

Claims

Claims1. An ingestible capsule (11) configured for ingestion into a lumen (6) of a patient, the ingestible capsule (11) comprising: a capsule housing (12) with an interior (14), a medicament (8) located inside the interior (14) of the capsule housing (12), a tissue attachment mechanism (40) transferable from an inactive state into an active state in response to a detection of a first in vivo condition inside the lumen (6) of the patient, wherein when in the active state the tissue attachment mechanism (40) is configured to attach the ingestible capsule (11) to biological tissue (5) adjoining or enclosing the lumen (6), a medicament delivery mechanism (50) transferable from an idle state into a delivery state in response to a detection of a second in vivo condition inside the lumen (6) of the patient, wherein when in the delivery state, the medicament delivery mechanism (50) is configured to deliver the medicament (8) into at least one of the lumen (6) and the biological tissue (5).

2. The ingestible capsule (11) according to claim 1, wherein the medicament delivery mechanism (50) is exclusively transferable from the idle state into the delivery state when both of the following conditions are met: i) activation of the tissue attachment mechanism (40), and ii) detection of the second in vivo condition.

3. The ingestible capsule (11) according to claim 1 or 2, further comprising a detector arrangement (30) configured to detect at least one of the first in vivo condition and the second in vivo condition inside the lumen (6) of the patient.

4. The ingestible capsule (11) according to any one of the preceding claims, further comprising a controller (20) coupled to at least one of the tissue attachment mechanism (40) and the medicament delivery mechanism (50) and configured to trigger activation of at least one of the tissue attachment mechanism (40) and the medicament delivery mechanism (50), wherein upon activation of the tissue attachment mechanism (40) the tissue attachment mechanism (40) transfers from the inactive state into the active state and wherein upon activation of the medicament delivery mechanism (50) the medicament delivery mechanism (50) transfers from the idle state into the delivery state.

5. The ingestible capsule (11) according to claim 3 and 4, wherein the controller (20) is coupled to the detector arrangement (30) and wherein the controller (20) is operable to trigger activation of at least one of the tissue attachment mechanism (40) and the medicament delivery mechanism (50) in response to the detector arrangement (30) detecting at least one of the first in vivo condition and the second in vivo condition.

6. The ingestible capsule (11) according to any one of the preceding claims, wherein the first in vivo condition is one of a first predetermined temperature, a first predetermined pH value, a first predetermined enzymatic environment and a first predetermined electrical conductivity.

7. The ingestible capsule (11) according to any one of the preceding claims, wherein the second in vivo condition is one of a second predetermined temperature, a second predetermined pH value, a second predetermined enzymatic environment and a second predetermined electrical conductivity.

8. The ingestible capsule (11) according to any one of the preceding claims 3-7, wherein the detector arrangement (30) is configured to quantitatively measure at least one physiological parameter or physical parameter being indicative of or being related to at least one of the first in vivo condition and the second in vivo condition.

9. The ingestible capsule (11) according to any one of the preceding claims, wherein the tissue attachment mechanism (40) is transferable from the active state into the inactive state or into an inoperable state upon lapse of a predefined time interval since it has been activated and / or upon detection of a third in vivo condition inside the lumen (6) of the patient.

10. The ingestible capsule (11) according to any one of the preceding claims, wherein the tissue attachment mechanism (40) comprises at least one tissue attachment element (41) configured for fastening to the biological tissue (5), wherein the tissue attachment element (41) is at least one of deployable or movable relative to the capsule housing (12) into at least one of an extended or expanded configuration upon transferring the tissue attachment mechanism (40) from the inactive state into the active state.

11. The ingestible capsule (11) according to claim 9 and 10, wherein the tissue attachment element (41) is separable or detachable from the tissue attachment mechanism (40) upon detecting of the third in vivo condition inside the lumen (6) of the patient.

12. The ingestible capsule (11) according to any one of the preceding claims, wherein the medicament delivery mechanism (50) comprises a medicament reservoir (51) provided with the medicament (8) and a delivery unit (52), wherein the delivery unit (52) is connected to the medicament reservoir (51) in a medicament transferring manner.

13. The ingestible capsule (11) according to claim 12, wherein the delivery unit (52) comprises a drive mechanism (53) and a delivery element (54) connected to the medicament reservoir (51) and wherein the drive mechanism (3) is configured to expel the medicament (8) from the medicament reservoir (51) through the delivery element (54) into at least one of the lumen (6) or biological tissue (5).

14. The ingestible capsule (11) according to claim 12 or 13, wherein the delivery unit (52) comprises a tissue penetrating element (56) configured to penetrate or to pierce the biological tissue (5) for medicament delivery into the biological tissue (5).

15. The ingestible capsule (11) according to any one of the preceding claims, wherein the medicament delivery mechanism (50) is transferable from the delivery state into at least one of the idle state and an inoperable state in response to a detection of a fourth in vivo condition inside the lumen (6) of the patient.

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