HK40009964A - Ingestible capsule for the phototherapeutic treatment of infections - Google Patents

Description

Swallowable capsule for phototherapy treatment of infections

Technical Field

The present invention relates to the field of treating intestinal infections.

In particular, the present invention relates to a swallowable capsule for phototherapy treatment of Helicobacter pylori (Helicobacter pylori) infections.

Background

Helicobacter pylori (h. pylori) is a gram-negative microaerophilic bacterium that colonizes the mucus layers of the stomach and duodenum. The incidence of infection in the world population is higher than 50% and in developing countries up to 90%. Helicobacter pylori may cause various diseases such as chronic gastritis, gastric and duodenal ulcers, gastric lymphoma, adenocarcinoma, and non-digestive system diseases (extragenic diseases). Helicobacter pylori is also recognized by the world health organization as a class I carcinogen.

Currently, helicobacter pylori infections are treated with a drug therapy consisting of a proton pump inhibitor in combination with two or three antibiotics. The efficacy of drug therapy is reduced to 70% -85% due to various side effects and antibiotic resistance.

To overcome these limitations, we used methods based on bacterial photodynamic therapy (PDT). PDT was introduced at the beginning of the last century and was initially used to treat tumors. In conventional PDT, a non-toxic dye, known as an external photosensitizer, is injected or applied to the patient by topical administration, which selectively accumulates in the target (i.e., malignant tissue or bacteria). After about 48-72 hours, the lenses were exposed to visible light. In the presence of oxygen, the interaction between the photosensitizer and light results in the production of reactive oxygen species, thereby inducing cell death. The use of PDT to kill pathogenic microorganisms has attracted increasing attention by clinicians, and this system has been proposed as a therapy for a variety of topical infections.

Recent interest in PDT has returned primarily due to the growth of drug resistance that cannot be prevented, including many types of pathogens. For example, helicobacter pylori is known to be photolabile without exogenous uptake of a photosensitizer. In fact, helicobacter pylori naturally has photoactive porphyrins, coproporphyrins and protoporphyrin IX, which are natural photosensitizers. Thus, helicobacter pylori may be killed by exposing it to light having an appropriate wavelength.

WO2011055395 describes a swallowable capsule for specific phototherapy of helicobacter pylori infections, wherein the presence of at least a semi-reflective mirror is provided to increase the illumination provided by the therapeutic light source.

However, this solution is not very efficient, since it does not adapt to different regions of the stomach and therefore to different stages of the infection caused by the helicobacter pylori bacteria. Thus, with this device, the patient should take more than one capsule, each adapted to a different area of the stomach, which increases the cost of the treatment and makes it more complicated for an untrained user to perform.

WO2012123939a1 describes a swallowable capsule for phototherapy of the gastrointestinal tract of a patient, wherein the presence of one or more phototherapy light sources and a control unit adapted to activate the light sources is provided in order to administer a specific dose of therapeutic illumination in the gastrointestinal tract. Thus, the described capsule allows for more adaptive administration to different regions of the gastrointestinal tract.

However, this solution does not consider helicobacter pylori infection as a specific target and is not very effective in supporting this specific therapy for which WO2012123939a1 does not provide the necessary wavelengths and methods of administration.

In particular, although some wavelengths have been demonstrated to have efficacy for killing bacteria in vitro (m.r. hamblin, j.viviros, c.yang, a.ahmadi, r.a.ganz and m.j., Tolkoff "Helicobacter pylori accumulates photoactive porphyrins and is killed by visible light (Helicobacter pylori photoactive reactive microorganisms and killed by visible light)", "Antimicrobial active chemotherapy" (antibacterial active chemotherapy), volume 49, phase 7, page 2822-2827, month 2005 7), it should be taken into account that the distribution of bacteria in vivo is different and often distributed in a more complex manner. It must therefore be taken into account that bacteria must be treated in vivo in the human stomach, among other factors being fundamental, among others, for example the penetration depth of light at different wavelengths. In fact, the case of a stomach wall consisting of macrostructures (folds) and microstructures (fovea) is completely different from the case of irradiation of bacteria on Petri dishes (Petri dish) under in vitro conditions. The folds and pits are characterized by transverse dimensions of about 2-4mm and 100-200 μm, respectively, in which bacteria can cling and harbor. In general, the bactericidal efficiency in the real stomach is a multi-parameter problem, the parameters of which are presented by the optical properties of endogenous photosensitizers and the photophysical properties of the stomach (absorption spectrum and ROS production efficiency) and by the optical properties of the tissue, which can strongly influence the spectrum of effective wavelengths at which bacteria are killed. Taking into account the optical parameters of each layer of the gastric mucosa, the filtering effect of weaving on certain wavelengths must be considered to optimize the effectiveness of the photo-killing.

To optimize the phototherapy efficacy of small, swallowable devices, the selection of an optimal emission wavelength for an endoscopic capsule is essential for good bacterial eradication. The selection of the optimal spectral illumination band is essential to obtain an efficient photo-killing and an optimized energy management, rather than being used in photons of a wavelength different from the most efficient wavelength, also allowing a reduction in the number of treatment sessions, in which case said reduction in translation is effective in reducing the number of capsules required for treatment. The use of specific and non-random wavelengths allows the therapeutic efficacy of a single device to be increased by over 50% without wasting energy in photons that are not suitable for phototherapy of specific bacteria.

Furthermore, it is essential to dynamically select the wavelengths to be used, considering that the bacterial distribution in the stomach must be dynamic and affected by changes related to the infection state. It is known, for example, that helicobacter pylori, although having an adaptive system that allows it to survive in the acidic environment of the stomach, prefers an environment with a higher pH. Thus, it is possible to note that, in the acute colonization phase, helicobacter pylori is found only in the antrum. However, as the infection continues and you enter the chronic phase of gastritis or use, for example, antacids (antacids), the bacteria tend to localize themselves in the uppermost part of the stomach up to the body of the stomach. In the longest infected areas (antrum), the depth of the bacteria is deeper, while in the body and fundus areas, the bacteria are more superficial.

Both cited documents are not very effective in the treatment of helicobacter pylori, without taking into account the aspects described above.

Disclosure of Invention

It is therefore a feature of the present invention to provide a swallowable capsule for phototherapy treatment of helicobacter pylori infections, which allows for targeted and effective therapy in order to reduce the number of capsules to be taken.

Another feature of the present invention is to provide a swallowable capsule for phototherapy treatment of helicobacter pylori infections, which allows real-time adaptation to the different areas of the stomach to be treated and to the different conditions in which the bacteria may be located.

It is a further feature of the present invention to provide a swallowable capsule for phototherapy treatment of helicobacter pylori infections that allows for an optimized energy expenditure relative to prior art capsules in order to prolong the therapeutic effect of each capsule.

These and other objects are achieved by a swallowable capsule, which in use is arranged to pass through the stomach of a human being for phototherapy treatment arranged against infection due to the presence of the bacterium helicobacter pylori, comprising:

-at least one primary light source arranged to emit light having a wavelength λ₁Electromagnetic phototherapy waves of (a);

-at least one auxiliary light source arranged to emit light having a wavelength λ₂Electromagnetic phototherapy waves of (a);

-a package arranged to contain the or each primary light source and the or each secondary light source, the package being specific to the wavelength λ₁And λ₂At least partially transparent;

-a control unit arranged to selectively activate the or each primary light source and/or the or each secondary light source;

-at least one energy source arranged to provide energy for supplying the control unit and/or the light source;

said wavelength λ₁And λ₂So that 400nm < lambda₁< 525nm and 525nm < lambda₂＜650nm；

It is mainly characterized in that the control unit is further arranged to:

-receiving location information reporting in real time that the swallowable capsule passes through a region of the stomach;

-determining a wavelength, a dose and an administration duration of the electromagnetic phototherapy wave for optimal phototherapy treatment of the region of the stomach, knowing the location information;

-selectively activating the or each primary light source and/or the or each secondary light source to provide the optimal phototherapy treatment of the region of the stomach.

The advantage over the prior art is that it is possible to more effectively activate more phototherapeutic frequencies and manage their administration, thereby enabling the number of photons released (J/cm)²) Maximizing without requiring more capsules to be inserted into the stomach.

Advantageously, λ₂625nm and lambda₁500nm。

More specifically, in the first step, in the corpus-fundus region of the stomach, it is possible to have 20% of the emitted radiation from λ₁500nm and 80% of λ₂625nm in order to obtain more efficient and less penetrating radiation (in the vicinity of blue/green) for treating bacteria arranged on the surface.

In a second phase, when the capsule reaches the antrum region of the stomach, the ratio may be varied substantially gradually until inversion, reaching 80% of λ₁500nm and 20% of λ₂625nm so you can penetrate more into the mucus or between gastric folds.

Advantageously, the control unit is further arranged to receive information on the temperature of the light source, which allows determining the duration of application of the electromagnetic phototherapy wave to allow a lower consumption of energy supplied by the energy source.

In particular, knowing the temperature of the light source, the control unit can activate and deactivate said light source in order to optimize the ratio between the emitted radiation and the dispersed energy. In fact, it is known that the operating temperature affects the luminous efficiency of the LED (for some types of LED, the relative luminous efficiency is 100% at 20 ℃, 80% at 40 ℃ and 60% at 60 ℃, and this varies according to the wavelength and the type of light source used).

For example, if the operating temperature rises too much, the luminous efficiency may be negatively affected, and it may therefore be more convenient to switch the light source on and off, rather than keep it permanently switched on. In this way the average luminous efficiency (photons illuminated within a time unit) will become almost constant and in any case greater than in the case where there is no control. In this way, the performance in terms of the therapeutic efficacy of the individual devices will be further improved, given that the dynamic selection of wavelengths driven by the operating temperature of the device and its position allows the therapeutic efficacy of the individual light sources to be improved. In order to always lower the temperature of the light source and increase the energy efficiency, the control unit (depending on the temperature sensor) may decide to switch off some LEDs not used at the time.

Advantageously, a pH detector is also provided, configured to measure a pH level in an environment surrounding the swallowable capsule to provide the location information to the control unit.

Specifically, a more acidic environment would indicate that the capsule is in the antrum of the stomach, while a less acidic environment would indicate that the capsule is in the cecum.

Some reference values of pH are as follows:

-esophageal pH 5-6

Fundus pH 4-5

-gastric body pH 3-4

Antrum pH 1-2

-duodenal pH 7-8

In particular, inertial sensors are also provided, arranged to determine linear and angular velocities and accelerations of the swallowable capsule to provide the position information to the control unit.

The dynamic selection of the wavelength by the control unit and its optimized ignition management may also be based on the positioning of the capsule or its speed. Likewise, in some cases it may be possible to select some wavelengths and some LEDs that are less intense (e.g. at the end of the treatment when the capsule is about to pass through the stomach and is therefore definitely in the antrum position where lumen is limited and no light needs to be administered).

Furthermore, based on the information from the inertial sensor (which shows the path formed by the capsule and its spatial orientation), it would also be possible to select the number and type of light sources to be activated and the relative administered dose (which may be reduced if the capsule is fixed at one point). In this way, it is possible to know the path formed by the capsule and its spatial orientation. The control unit may determine the dose to be administered from the location, while depending on the orientation, it may select which light sources to activate.

In particular, at least one magnetic sensor configured to measure a magnetic signal from the stomach to provide the position information to the control unit is also provided. In this way, by placing the magnet/electromagnet at a predetermined position outside the user's body, the magnetic sensor allows the position of the capsule to be established based on the strength and direction of the magnetic signal.

Advantageously, at least one proximity sensor is also provided, configured to measure the proximity of the wall of the stomach to the swallowable capsule. In this way, the control unit may switch off the light source opposite the wall if the capsule is attached to the wall.

By combining the positioning information from the magnetic sensor and the orientation information from the proximity sensor, it is thus possible to establish whether it is convenient to switch on or off the LEDs in a particular region of the capsule relative to other regions.

Advantageously, the or each primary light source and the or each secondary light source are placed in the transparent package.

In particular, the or each primary light source and the or each secondary light source comprise organic and flexible diodes.

Advantageously, a diffusing fluid is provided within the transparent package, the diffusing fluid being arranged to increase diffusion of the light source. In this way, maximum angular coverage of the light radiation in the vicinity of the capsule is possible.

Furthermore, the transparent package may comprise a light guide arranged to convey the electromagnetic phototherapy waves along a predetermined trajectory.

Advantageously, a ferromagnetic and/or magnetic element is also provided for allowing the swallowable capsule to be guided in the stomach by means of a magnet or electromagnet outside the stomach. The ferromagnetic element may also be the battery itself if present inside the capsule.

In particular, an apparatus for receiving energy through wireless transmission is provided. It may for example be a winding that also serves as an electromagnet that is remotely driven by means of a magnet.

Rather, the main part of the capsule may be a battery located inside the capsule itself.

To this end, a winding system may be added or replaced to remotely supply energy to the capsule. One possibility could be to guide the capsule at a specific point by means of a magnetic system or using external electromagnets to maximize the continuous or discontinuous energy transfer, to allow the same capsule to continue the treatment for a longer time than it takes on average in the stomach.

In this way, thanks to the invention, the single device can be irradiated, when necessary and in a variable manner with respect to the wavelength selected and identified by the control unit, as is the case with active ingredient management in drugs. The device makes it possible to illuminate the same point of the stomach with light of different colours, specifically chosen, so as to overcome the problem of random movements of the stomach which would otherwise not allow the proper illumination of some stomach areas, thus reducing the effectiveness of the treatment.

Specifically, the therapy combined with the selected wavelengths allows:

as regards the reduction of the number of capsules that the patient must take and then the reduction of the risks associated with each capsule immediately plays a role;

the advantage of making it possible to compose all wavelengths in a controlled manner, making it possible in the future to achieve the best possible compromise in terms of photodynamic therapy by means of the capsule.

In addition, in view of the presence of the control unit, the capsule is able to release a "variable dose combination" related to a multi-parameter analysis with respect to the passage of time, with respect to the variation of pH, with respect to the presence of an external magnetic field, based on proximity sensors and accelerometers, for optimal management of the energy source.

Drawings

Further characteristics and/or advantages of the invention will become clearer from the following description of an exemplary embodiment thereof, given by way of illustration and not of limitation, with reference to the attached drawings, in which:

fig. 1 shows a first exemplary embodiment of a swallowable capsule according to the present invention, wherein 4 light sources are provided;

fig. 2 shows a second exemplary embodiment of a swallowable capsule according to the present invention, wherein a plurality of light sources are provided;

fig. 3A, 3B, 3C and 3D show other exemplary embodiments of swallowable capsules having different component forms and arrangements.

Detailed Description

Referring to fig. 1, in a first exemplary embodiment, a swallowable capsule 100 according to the present invention comprises two primary light sources 110 arranged to emit light having a wavelength λ and two secondary light sources 120₁The auxiliary light source being arranged to emit electromagnetic light having a wavelength λ₂The electromagnetic phototherapy wave of (1). Swallowable capsule 100 then contains a package 130, which isFor wavelength lambda₁And λ₂At least partially transparent and arranged to accommodate light sources 110 and 120. There is also a control unit 140 arranged to selectively activate the light sources 110 and 120, and an energy source 150 arranged to provide energy for supplying the control unit 140 and the light sources 110 and 120.

In fig. 2, a second exemplary embodiment is shown, in which there are a plurality of light sources 110 and 120 alternating with each other along the entire circumference of the capsule. Thus, it is highly probable that the capsule 100, independent of its position and orientation within the stomach, can emit effective light waves, i.e., to the desired therapeutic target.

In fig. 3A, 3B, 3C and 3D, some exemplary embodiments of capsules are shown with different forms of packaging 130, and thus different arrangements of internal components.

The foregoing description of some exemplary embodiments will so fully reveal the invention according to the conceptual point of view, so that others, by applying current knowledge, will be able to modify and/or adapt for various applications such exemplary embodiments without additional research and without departing from the invention, and, therefore, it is intended that such adaptations and modifications will have to be considered as equivalent to the specific embodiments. The components and materials that fulfill the different functions described herein may have different properties without for this reason deviating from the field of invention. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation.

Claims (8)

1. A swallowable capsule (100) configured, in use, to pass through a human stomach for phototherapy treatment configured to combat infection due to the presence of the bacterium helicobacter pylori, the swallowable capsule (100) comprising:

at least one primary light source (110) arranged to emit light having a wavelength λ₁Electromagnetic phototherapy waves of (a);

at least one auxiliary light source (120) arranged to emit light having a wavelength λ₂Electromagnetic phototherapy waves of (a);

a package (130) arranged to contain the or each primary light source (110) and the or each secondary light source (120), the package (130) being for the wavelength λ₁And λ₂At least partially transparent;

a control unit (140) arranged to selectively activate the or each primary light source (110) and/or the or each secondary light source (120);

at least one energy source (150) arranged to provide energy for supplying the control unit (140) and/or the light source (110, 120);

said wavelength λ₁And λ₂So that 400nm < lambda₁< 525nm and 525nm < lambda₂＜650nm；

The swallowable capsule (100) is characterized in that the control unit (140) is further arranged to:

receiving location information reporting in real time that the swallowable capsule (100) passes through a region of the stomach;

determining a wavelength, dose, and duration of administration of the electromagnetic phototherapy wave for optimal phototherapy treatment of the region of the stomach with knowledge of the location information;

selectively activating the or each primary light source (110) and/or the or each secondary light source (120) to provide the optimal phototherapy treatment of the region of the stomach.

2. A swallowable capsule (100) as claimed in claim 1, whereinAnd is

3. A swallowable capsule (100) according to claim 1, wherein the control unit (140) is further arranged to receive information on the temperature of the light source (110, 120), the information on the temperature allowing to determine the duration of administration of the electromagnetic phototherapy wave to allow a lower consumption of energy supplied by the energy source (150).

4. A swallowable capsule (100) according to claim 1, wherein a pH detector is further provided, the pH detector being configured to measure a pH level in an environment surrounding the swallowable capsule (100) to provide the location information to the control unit (140).

5. A swallowable capsule (100) according to claim 1, wherein inertial sensors are further provided, said inertial sensors being arranged to determine linear and angular velocities and accelerations of said swallowable capsule (100) to provide said position information to said control unit (140).

6. A swallowable capsule (100) according to claim 1, wherein at least one proximity sensor is further provided, said proximity sensor being configured to measure the proximity of a wall of the stomach to the swallowable capsule (100).

7. A swallowable capsule (100) according to claim 1, wherein a diffusing fluid is provided within the transparent package (130), the diffusing fluid being arranged to increase diffusion of the light sources (110, 120).

8. A swallowable capsule (100) according to claim 1, wherein the transparent package (130) comprises a light guide arranged to convey the electromagnetic phototherapy wave along a predetermined trajectory.