WO2016155671A1 - Dispositif ingérable - Google Patents

Dispositif ingérable Download PDF

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Publication number
WO2016155671A1
WO2016155671A1 PCT/CN2016/078405 CN2016078405W WO2016155671A1 WO 2016155671 A1 WO2016155671 A1 WO 2016155671A1 CN 2016078405 W CN2016078405 W CN 2016078405W WO 2016155671 A1 WO2016155671 A1 WO 2016155671A1
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WO
WIPO (PCT)
Prior art keywords
needle
swallowable device
outer casing
attachment member
capsule
Prior art date
Application number
PCT/CN2016/078405
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English (en)
Chinese (zh)
Inventor
傅君志
Original Assignee
傅君志
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 傅君志 filed Critical 傅君志
Publication of WO2016155671A1 publication Critical patent/WO2016155671A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body

Definitions

  • the present invention relates to a swallowable device. More specifically, the present invention relates to a swallowable drug delivery device.
  • a swallowable device that can be used to deliver a drug in the gastrointestinal tract.
  • a swallowable device such as a swallowable capsule, is provided for delivering a drug into a tissue, such as the wall of the stomach, the wall of the small intestine, the wall of the large intestine, or the wall of other gastrointestinal organs.
  • the apparatus, system, kit and square of the present invention The method can be used to deliver any drug suitable for delivery to the wall of the stomach, the wall of the small intestine, the wall of the large intestine or other gastrointestinal organs.
  • the devices, systems, kits and methods of the invention are useful for delivery in the gastrointestinal tract that are difficult to absorb, poorly tolerated, and/or subject to biological/chemical degradation (eg, by digestive enzymes in the gastrointestinal tract and/or Or acid decomposition) of the drug.
  • the devices, systems, kits and methods of the invention can be used to deliver drugs that were previously only or preferably administered by parenteral administration, such as intravenous or intramuscular injection.
  • the devices, systems, kits and methods of the invention can be used to achieve rapid release of a drug into the bloodstream by oral delivery.
  • a swallowable device for delivering a drug into a tissue.
  • the device includes a housing sized for swallowing, an attachment member, a drug, a penetrating member, and an actuation member, wherein the drug, the first configured penetration member and the actuation member are located inside the housing, and the attachment member is located on the outer surface of the housing.
  • a swallowable device comprising:
  • An attachment member on an outer surface of the outer casing adapted to attach the swallowable device to an external tissue
  • An actuating member located inside the outer casing having third and fourth configurations respectively adapted to the first and second configurations of the penetrating member, wherein the actuating member is from the third configuration
  • the penetrating member is driven to change from the first configuration to the second configuration when the fourth configuration is changed, and the drug is driven to be output via the penetrating member.
  • the attachment member is overcoated with a degradable coating.
  • At least one through hole is provided on the outer casing adjacent the actuating member, and the through hole is optionally shielded with a degradable shielding layer.
  • the coating layer degrades faster than the degradation rate of the masking layer.
  • the penetrating member includes a needle-shaped body that supports the needle-shaped body, the needle-shaped body is adjacent to the attachment member and the needle tip direction is toward the swallowable device On the outside, the needle-shaped body contains a drug; the actuating member is located between the support and a side of the outer casing opposite the attachment member.
  • the needle is provided with a barb.
  • the actuation component comprises an expandable element.
  • the actuation component includes an elastomer and a degradable stop component coupled to the outer casing and/or the support such that the elastomer is in a compressed state.
  • the outer periphery of the support is coupled to a skirt, the outer edge of the skirt abutting the inner surface of the outer casing.
  • the outer casing includes an internal volume and can be made from a variety of biocompatible polymers known in the art, such as various biodegradable polymers.
  • the outer shell can be controllably degraded into smaller pieces to facilitate passage of the swallowable device through the gastrointestinal tract and excretion and/or absorption.
  • the outer shell may comprise a suture of biodegradable material that is controllably degraded to produce an outer size piece of optional size and shape to facilitate its passage through the gastrointestinal tract.
  • the suture can be pre-stressed, perforated, or otherwise treated to accelerate degradation.
  • the outer casing is integrally formed of a biodegradable material and has grooves or depressions on the inner or outer surface of the outer casing such that the outer casing first degrades at the grooves or depressions, resulting in an optional The outer size of the size and shape of the piece to facilitate the swallowable device through the gastrointestinal tract.
  • the outer casing further includes one or more openings.
  • Part or all of the penetrating member of the swallowable device can extend out of the housing through the opening and into the tissue.
  • the opening has a degradable coating.
  • the cladding layer can be configured to degrade in various ways in response to various conditions.
  • the coating may be made of a biodegradable material configured to be degraded in whole or substantially all by body fluid in response to higher pH or other conditions within the small intestine.
  • the coating may completely enclose the opening such that the digestive juice cannot enter the interior of the housing until the swallowable device has reached a predetermined position.
  • the outer casing is integral with the portion adjacent the penetrating member. As the penetrating member of the swallowable device changes from the first configuration to the second configuration, the penetrating member penetrates the outer casing, thereby partially or fully extending out of the outer casing and into the tissue.
  • the attachment component of the swallowable device is located on the outer surface of the outer casing for attaching the swallowable device to a tissue surface, such as the surface of the gastrointestinal tract.
  • the attachment component can be attached to the tissue surface in a variety of ways.
  • the attachment component is an adhesive layer, such as various bioadhesives known in the art, to bond the swallowable device to the tissue surface.
  • the swallowable device can be bonded to different tissues by adjusting the composition of the adhesive.
  • the adhesive can be an adhesive that has strong adhesion only under acidic conditions, thereby allowing the swallowable device to adhere to the stomach tissue.
  • the adhesive may be an adhesive that has strong adhesion only under alkaline conditions, thereby allowing the swallowable device to adhere to the intestinal tissue.
  • the adhesive loses adhesion or is decomposed after bonding to the tissue surface for a period of time, thereby allowing the swallowable device to detach from the tissue surface.
  • the adhesive is configured to lose adhesion or be decomposed in response to the location of the swallowable device, such as due to hydration or loss of adhesion or decomposition upon exposure to pH or other chemical conditions within the gastrointestinal tract.
  • the attachment member comprises a hook.
  • the hooks may be one or more that extend upright on the outer surface of the outer casing away from the outer casing.
  • the hook has a stem connected to the outer casing and a head connected to the stem.
  • the projection of the head on the surface of the outer casing at least partially extends beyond the stem, for example in the form of a hook, an arrow or a mushroom.
  • the hook portions of adjacent hooks may protrude in the same or different directions.
  • Each of the adjacent hooks may have a flat surface that faces each other in a face to face relationship.
  • the hook forms a hook-and-loop fastening system with the outer tissue to attach the swallowable device to the outer tissue.
  • the attachment member further includes a substrate between the hook and the outer casing.
  • the attachment components of the swallowable device can be made of a degradable material such as PGLA, cellulose, and the like.
  • the attachment member is located adjacent the end of the penetrating member and is located on the outer surface of the respective outer casing.
  • the attachment member can be located around the opening when the swallowable device has an opening in the housing through which the penetrating member passes.
  • the swallowable device after adhering to the tissue, penetrates the end of the component proximate to the tissue such that the penetrating member can penetrate into the tissue after extending out of the outer shell. In this way, the drug in the swallowable device can enter all or substantially all of the tissue, resulting in a stable and controllable delivery effect.
  • the surface of the attachment member has a coating.
  • the cover layer covers all or substantially all of the attachment members such that the attachment members do not have an attachment function in the initial state.
  • the coating may be made of a degradable material and degraded after the swallowable device is swallowed.
  • the degradation rate of the coating is higher than other portions of the swallowable device, such as substantially degraded before the swallowable device reaches the desired location or is about to reach the desired location, such that the swallowable device It can be attached to the surface of the tissue and deliver the drug.
  • the penetrating member of the swallowable device can include a needle or other similar structure having a lumen or other compartment and a needle for penetration into a selectable depth in the wall of the gastrointestinal tract.
  • the device of the present invention can include one or more penetrating members, including, for example, a second penetrating member, a third penetrating member, and a greater number of penetrating members.
  • Each penetrating member can be used to deliver the same or different drugs.
  • each worn The transmissive members may be distributed in different directions with respect to the long or short axis of the outer casing, or the penetrating members may be concentrated in one direction.
  • the penetrating member includes a needle and a support that are integrally connected, the needle of the needle being adjacent to the attachment member and having a tip direction toward the outside of the swallowable device.
  • the needle is hollow with a conduit connected to at least one opening in the support.
  • the swallowable device of the present invention further includes a sachet adjacent the needle and the support, the bladder being sealingly coupled to the support and in fluid communication with a conduit in the needle.
  • the penetrating member of the swallowable device has a first configuration and a second configuration.
  • the penetrating member When the penetrating member is in the first configuration, it is in a normal sense or in an initial state, in which case all or substantially all of the penetrating member is located inside the casing.
  • the penetrating member When the penetrating member is in the second configuration, it is in a normal sense of use, when the swallowable device has been swallowed into the body and all or part of the penetrating member is located outside the casing and penetrates into the target tissue . By penetrating the component, the drug in the swallowable device enters the tissue.
  • the actuation member is coupled to at least one of the penetration member and the medicament.
  • the actuation member is configured to drive the penetration member to change from the first configuration to the second configuration such that it partially or fully enters the interior of the tissue, such as the gastrointestinal wall.
  • the actuation component is configured to drive the drug through the penetrating component to deliver the drug into the tissue, such as the gastrointestinal wall.
  • the actuation member is configured to withdraw the penetrating member from the tissue after pushing the drug through the penetrating member into the tissue.
  • the actuating member is configured to retain the penetrating member within the tissue.
  • the actuation component of the swallowable device has a third configuration and a fourth configuration.
  • the actuating member When the penetrating member of the swallowable device is in the first configuration, the actuating member has a third configuration that is adapted thereto.
  • the actuation member changes from the third configuration to the fourth configuration, the drive penetration member changes from the first configuration to the second configuration, and the drug is driven through the penetration The component is output to the outside of the casing.
  • the stop member is coupled to the outer casing and/or the support such that the elastomer is in a compressed state. Degradation of the stop member causes the elastomer to be released, thereby driving the penetrating member to change from the first configuration to the second configuration and driving the drug out of the outer casing via the penetrating member.
  • the outer periphery of the support is coupled to a skirt, the outer edge of the skirt abutting the inner surface of the outer casing such that the elastomer is in a compressed state. Degradation of the skirt causes the elastomer to be released, thereby driving the penetrating member to change from the first configuration to the second configuration and driving the drug out of the housing via the penetrating member.
  • the actuating member is located between the support and the side of the housing opposite the attachment member.
  • the actuating member comprises an expandable member.
  • the expandable element is, for example, an expandable material, a balloon or other expandable element.
  • An expandable element is provided inside the outer casing, which is optionally coupled to the penetrating member.
  • the expandable member is located inside the outer casing and the outer casing has a through hole adjacent the expandable member. Body fluid can enter the swallowable through the through hole Inside the device, in contact with the expandable element.
  • at least a portion of the surface of the outer shell comprising the through holes is desirably coated with a masking layer, such as an enteric polymer layer. The masking layer can be degraded in response to various conditions such as pH conditions.
  • the shielding layer provides a protective seal over the through hole such that the digestive fluid cannot enter the interior of the outer casing such that the expandable member expands until the swallowable device has reached a predetermined position.
  • a degradable masking layer on the aperture provide the primary means and means of ensuring that the swallowable device does not extend and/or deploy its penetrating member prior to reaching the target tissue. .
  • the expansion of the expandable member pushes the penetrating member into the tissue.
  • the expansion of the expandable member also pushes the drug into the tissue.
  • the maximum expanded volume of the expandable member can be configured to exceed the volume of the outer casing such that after expansion, the outer casing is ultimately expanded into one or more pieces to facilitate passage through the intestine.
  • the swellable material comprises a swellable polymer that is variable in volume under specific conditions, such as a superabsorbent polymer (SAP).
  • SAP superabsorbent polymer
  • Superabsorbent polymers are a class of macromolecules containing hydrophilic groups and crosslinked structures, including starches (grafts, carboxymethylates, etc.), celluloses (carboxymethylation, grafts, etc.). And synthetic polymers (polyacrylic, polyvinyl alcohol, polyoxyethylene, etc.) and other types. Before the water absorption, the chains of the superabsorbent polymer are entangled with each other and crosslinked into a network structure, thereby achieving an overall compactness and a small volume.
  • the expandable member includes a bladder and a degradable valve that divides the bladder into two first and second chambers that are isolated from one another.
  • the bladder In the first configuration, the bladder is typically located within the outer casing in an at least partially non-expanded state.
  • the capsules can be made from a variety of biocompatible polymers known in the art. Desirably, the bladder has a thin wall, such as less than about 0.01 centimeters.
  • the first chamber and the second chamber store the first reactant and the second reactant, respectively.
  • an acid such as citric acid and a base such as sodium carbonate may have a suitable ratio, for example, about 2:1.
  • the reactants may also include other acids such as acetic acid and bases.
  • the first reactant and the second reactant may each independently comprise a plurality of different components.
  • the first reactant and the second reactant mix and cause the volume of the bladder to expand, such as by generating a gas such as carbon dioxide.
  • the volume expansion produced by the first reactant and the second reactant can be configured to be greater than the maximum volume of the bladder such that upon expansion, the bladder is ultimately expanded into one or more pieces, To make it easier to pass through the intestines.
  • the valve can be configured to open in various ways in response to various conditions.
  • the valve can be configured to open by degrading one or more portions in response to higher pH or other conditions within the small intestine.
  • the valve will be placed in the center of the bladder, but it can be placed in other locations.
  • the valve can have a beam-like structure that is placed within the outer casing to compress the portion of the bladder between the first chamber and the second chamber.
  • the beam can be attached to the inner surface of the outer casing at one or both ends.
  • the beam is attached to the radial side of the outer casing using an interference fit such that the beam can be snapped into place using pick and place methods and other similar methods known in the art of fabrication.
  • valve may include one or more hooping features, such as ridges that engage grooves or other mating features on the inner surface of the outer casing to apply additional to the balloon wall under the hoop feature. Force and apply a redundancy to the seal.
  • the valve can include a constricted section of the expandable element having a cover hoop made of a biodegradable material. This ring keeps the valve closed and opens the valve when it degrades.
  • the valve can be located in multiple locations within or on the housing for exposure to body fluids and degradation by body fluids. At least a portion of the valve can be exposed to the surface of the outer casing. Alternatively, the valve may also be located inside the housing, and the housing has a through hole near the valve where the valve is exposed to body fluid entering through the through hole. In one aspect of the invention, at least a portion of the surface of the outer shell comprising the through-holes is desirably coated with a masking layer, such as an enteric polymer layer, which can be degraded in response to various conditions, such as pH conditions. The shielding layer provides a protective seal over the through hole to prevent the digestive fluid from entering the interior of the housing to begin the degradation valve until the swallowable device has reached the predetermined position.
  • a masking layer such as an enteric polymer layer
  • embodiments employing a degradable protective layer on the holes and on the degradable valve provide for ensuring swallowing
  • the pharyngeal device does not extend and unfold its primary means and aids to penetrate the component prior to reaching the target tissue.
  • the valve can also be configured to open in response to a compressive force applied by peristaltic contraction within the small intestine.
  • the valve may be a time delay release valve that is configured to open after a certain period of time after an activation step initiated by the patient, such as peeling off a label or pressing a button.
  • the bladder or other expandable member can generally also include a retraction valve for contracting the expandable member after it has expanded.
  • the retraction valve can comprise a biodegradable material configured to degrade upon exposure to fluid in the small intestine and/or liquid within one of the balloon chambers to form an opening or passage for gas selection within the balloon .
  • the contraction valve can include a biodegradable portion at the end of the balloon to connect the opposite ends of the balloon wall together. In one aspect of the invention, when the degradable segment degrades due to exposure to a liquid, the balloon wall tears or otherwise breaks, thereby ensuring a high degree of rapid contraction.
  • the outer shell can be split into two or more pieces by configuring the expanded balloon to expose the large balloon segment directly to the degrading fluid in the small intestine. In order to promote the degradation of the valve. This can be accomplished by making the outer casing from separate parts, such as the two halves that are mechanically joined together, and/or by using the sutures described herein.
  • one or more piercing elements can be attached to the inner surface of the outer casing wall to be contacted and pierced by the piercing element when the bladder is fully retracted.
  • one or more tissue penetrating members can be coupled directly to the balloon and configured to be torn from the balloon when they are disengaged, thereby tearing the balloon wall during the process.
  • the activation component can include a film or peg that retains the penetrating component within the outer casing.
  • the tissue penetrating member is coupled to the spring loaded actuation member such that when the activation member is sufficiently degraded, it releases the penetrating member, which in turn pops out of the housing to penetrate into the tissue.
  • the shape of the activation member can function as a latch that holds the penetrating member in place.
  • the activation component can be located external or internal to the housing. In embodiments located inside the outer casing, the outer casing is configured to allow bodily fluids to enter the interior of the outer casing to allow degradation of the activation components.
  • the senor can include a strain gauge or other pressure/force sensor for detecting the number of peristaltic contractions experienced by the outer casing at a particular location within the intestinal tract.
  • the outer casing is sized such that it can be clamped by the small intestine during peristaltic contraction.
  • the small intestine has a contraction between 12 and 9 times per minute, which frequency gradually decreases along the length of the intestine.
  • the detection of the number of peristaltic contractions can be used to determine the relative position of the outer casing within the gastrointestinal tract.
  • a user of the swallowable device can externally activate the actuation member to deliver the drug via an RF device, a magnetic device, or other wireless signaling device known in the art.
  • a user may use a handheld device (eg, a handheld RF device) that includes not only signaling devices, but also for when the swallowable device is in the small intestine or gastrointestinal The device that notifies the user when other locations in the track.
  • a handheld device eg, a handheld RF device
  • the device that notifies the user when other locations in the track.
  • the same handheld device can also be configured to alert the user when the actuation member has been activated and one or more selected medications have been delivered. In this way, the user is confirmed that the drug has been delivered. This allows the user to take other appropriate medications and make other relevant decisions (eg, whether the diabetic has eaten and what food should be consumed).
  • the handheld device can also be configured to send a signal to the swallowable device to manipulate the actuation member and thereby prevent, delay or accelerate drug delivery. In use, such embodiments allow the user to intervene to prevent, delay, or accelerate drug delivery based on other symptoms and/or patient behavior (eg, eating, sleeping, exercising, etc.).
  • the user can also activate the actuation member from the outside for a selected period of time after swallowing the housing.
  • This period of time may be related to the typical transit time or passage time range through which the food moves through the gastrointestinal tract of the user to a particular location within the gastrointestinal tract.
  • the medicament of the swallowable device can be configured in the form of a liquid, semi-liquid or solid or any combination thereof.
  • the solid form of the drug may include a powder or a pill.
  • the semi-liquid may include a slurry, a paste, a gel, or the like.
  • the medicament of the swallowable device can be contained directly in the cavity of the outer casing.
  • the medicament can be contained within a closed medicament container.
  • the swallowable device can include more than one drug, for example, including a first drug, a second drug, a third drug, or more. These drugs may be included separately or collectively in a cavity within the outer casing, or each separately or collectively contained in a separate reservoir within the outer casing body.
  • a swallowable device can be used to deliver a variety of therapeutically effective amounts of the drug.
  • these drugs include various macromolecular peptides and proteins that would otherwise require injection due to their chemical breakdown in the stomach/gastrointestinal tract, for example, growth hormone, parathyroid hormone, insulin, interferon and others. A similar compound.
  • Suitable drugs that can be delivered by swallowable devices include various chemotherapeutic agents (eg, interferons), antibiotics, antivirals, insulin and related compounds, glucagon-like peptides (eg, GLP-1, Exenatide) , parathyroid hormone, growth hormone (eg, IFG and other growth factors), anti-epileptic agents, immunosuppressive agents, and various anti-like agents An anti-parasitic agent such as a malaria agent.
  • chemotherapeutic agents eg, interferons
  • antibiotics eg, antivirals, insulin and related compounds
  • glucagon-like peptides eg, GLP-1, Exenatide
  • parathyroid hormone eg, growth hormone (eg, IFG and other growth factors)
  • anti-epileptic agents eg, IFG and other growth factors
  • immunosuppressive agents e.g, anti-parasitic agent
  • An anti-parasitic agent such as a malaria agent.
  • the pharmaceutical composition can be incorporated into the swallowable device of the present invention for delivery to a user.
  • the drug can be incorporated into a pharmaceutical composition suitable for administration to a user with the device of the present invention.
  • these pharmaceutical compositions include pharmaceutically active ingredients, as well as a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carrier includes any solvent that is physiologically compatible, dispersion media, bactericidal and fungicidal agents, isotonic and absorption delaying agents, and the like.
  • pharmaceutically acceptable carriers include one or more of water, saline, phosphate buffer, dextrose, glycerol, ethanol, and the like, and combinations thereof.
  • isotonic agents for example, sugars, polyols (such as mannitol, sorbitol) or sodium chloride, may be included in the compositions.
  • the pharmaceutically acceptable carrier may also include minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers which enhance the shelf life or effectiveness of the drug.
  • compositions for use in the methods and compositions of the present invention may be adapted to a variety of different forms for administration by the devices of the present invention, including, for example, liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions.
  • liquid solutions e.g., injectable and infusible solutions
  • dispersions or suspensions e.g., dispersions, dispersions or suspensions.
  • compositions typically must be sterilized and stable under the conditions of manufacture and storage.
  • the compositions may be formulated as solutions, microemulsions, dispersions, liposomes or other ordered structures suitable for high drug concentrations.
  • the sterilized injection solution can be prepared by incorporating the required amount of the pharmaceutically active ingredient into a suitable solvent, which contains one of the above-listed components or a combination thereof as needed, followed by filter sterilization.
  • dispersions are prepared by incorporating the active compound into a sterilized carrier liquid containing the base dispersion medium and the additional ingredients enumerated above.
  • the preferred preparation methods are vacuum drying and lyophilization, yielding a powder from the active component of the pre-filter sterilized solution and any desired component.
  • the proper fluidity of the solution can be maintained, for example, by the use of a coating such as lecithin, by the required particle size in the case of dispersion, and by the use of surfactants.
  • Prolonged absorption of the injectable compositions can be brought about by the inclusion in the compositions in the compositions, such as,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
  • a variety of drugs can be delivered using a swallowable device to treat various conditions or conditions.
  • a swallowable device can be used to deliver multiple protease inhibitors to treat Treat AIDS. This allows the patient to take multiple medications for a condition or condition, but only once using the device of the present invention.
  • the swallowable device solves this problem by controlling the timing of delivery of various drugs.
  • two or more drugs of one treatment regimen are delivered and absorbed into the bloodstream or target tissue at specific time intervals or simultaneously. method. This improves the pharmacokinetics of the various target drugs and thus improves their efficacy.
  • the various portions of the swallowable device can each be independently fabricated from a suitable material, such as from the same or different biodegradable materials.
  • portions of the swallowable device can be independently made of the same or different materials that are not biodegradable but are not harmful to the user.
  • biodegradable material generally refers to a material whose chemical structure can be altered by a conventional environment, such as substances in the physiological environment of a human body, such as enzymes, pH, and natural compounds, to produce a simple element or chemical structure. So harmless. Biodegradable materials can also be bioerodible.
  • bioerodible means that the material is biodegradable, digestible or erosive in the environment, or is soluble or degradable into a reduced size material, for example, by chemical, biological (eg enzymatic), physical decomposition, Or solubilization, so that the material is eliminated from the environment without major harm.
  • biodegradable as used herein also encompasses the term “bioabsorbable”, which generally describes a material whose decomposition products that decompose under physiological conditions can enter a host subject to undergo biological activity. Absorption, for example, a metabolite of the biochemical system that becomes the host object.
  • biodegradable materials may include gelatin, sodium alginate, cellulose esters (such as hydroxypropylmethylcellulose, etc.), plant polysaccharides (such as pullulan, fucoidan, carrageenan, agar, etc.) and starch. And its derivatives (such as modified starch, etc.).
  • Degradation of the various components caused by one or more conditions in the gastrointestinal tract can be achieved by selecting the ingredients of the materials used in the various components of the swallowable device, the degree of crosslinking of these components, the thickness, and other conditions. Similarly, the order of degradation of each component can be controlled thereby, thereby appropriately functioning the various parts. The function of the piece reaches the intended purpose of the swallowable device. For example, less cross-linking and/or thinner gauges can increase the rate of degradation and vice versa.
  • copolymerization or otherwise mixing one or more polymers can result in a number of specific material properties in addition to biodegradation, such properties including, but not limited to, stiffness, strength, flexibility, and hardness.
  • the coating of the clad attachment member degrades faster than the degradation layer of the obscuring through-hole.
  • the attachment member is exposed in the gastrointestinal tract cavity, and the through hole is also shielded by the shielding layer, so that the swallowable device can be attached to the surface of the gastrointestinal tissue, and the actuating member is
  • the penetrating members are still wholly or substantially entirely inside the casing.
  • the shielding layer is degraded, and the body fluid enters the outer casing of the swallowable device through the through hole, so that the actuating member is changed from the third configuration to the fourth configuration, and the driving and penetrating member is changed from the first configuration to the second configuration, and the driving device is driven
  • the drug is output into the gastrointestinal tissue via the penetrating member.
  • the drug in the swallowable device can be all or substantially all exported to the gastrointestinal tissue via the penetrating member.
  • the rate of degradation of the attachment member, outer shell, bladder, and the like of the swallowable device is lower than the rate of degradation of the cover layer and the masking layer.
  • the penetrating member of the swallowable device can also be configured to degrade after the drug in the swallowable device is exported to the gastrointestinal tissue, for example, at intervals of two administrations, such that the previously administered swallowable The device does not affect the administration of the subsequent swallowable device.
  • the penetrating member of the swallowable device can be configured to have a higher stiffness for better penetration into tissue.
  • Materials having higher hardness and methods for their preparation are well known in the art, such as polymers having a relatively high degree of crosslinking.
  • Figure 1 is a schematic view of the swallowable capsule 100 in the intestine
  • Figure 2 shows a perspective view of the appearance of a capsule 200 of one embodiment
  • Figure 3 shows a perspective view of the appearance of a capsule 300 of one embodiment
  • Figure 4A shows the outer casing 402 in one embodiment, and Figure 4B shows the degraded outer casing piece;
  • Figure 5A shows a cross-sectional view of a capsule 500 of one embodiment
  • Figure 5B shows a cross-sectional view of a capsule 500' of one embodiment
  • Figure 6 shows a schematic cross-sectional view of a capsule 600 of one embodiment
  • Figure 7 shows a cross-sectional view of a capsule 700 of one embodiment
  • Figure 8 shows a schematic cross-sectional view of a capsule 800 of one embodiment
  • Figure 9A shows a schematic cross-sectional view of a capsule 900 of one embodiment
  • Figure 9B shows a schematic cross-sectional view of a capsule 900' of one embodiment
  • Figure 10 shows a schematic cross-sectional view of a capsule 1000 of one embodiment
  • Figure 11 shows a schematic cross-sectional view of a capsule 1100 of one embodiment
  • Figure 12 shows a schematic cross-sectional view of a capsule 1200 of one embodiment.
  • Figure 1 is a schematic illustration of the capsule 100 positioned within the intestinal tract.
  • the capsule 100 can be swallowed through the mouth and can be moved to the stomach or intestine via the digestive tract.
  • Hooks 108 are provided on the outer surface of one side of the capsule 100, and these hooks 108 serve as attachment members for attaching the capsule to the stomach wall or the intestinal wall.
  • FIG. 2 shows a perspective view of the appearance of a capsule 200 of one embodiment.
  • the appearance of the capsule generally appears as an oblong or olive shape.
  • An attachment member 210 composed of a plurality of hooks 208 is disposed on one side of the outer surface of the capsule.
  • the hook 208 engages the tissue of the stomach wall or the intestinal wall to effectively attach the capsule 200 to the stomach wall or the intestinal wall.
  • the hooks 208 in this example are arranged in a neat array.
  • the bending directions of the hooks 208 are not uniform. For example, the hooks 208 having the same bending direction in each of the two columns constitute one unit, and the hooks 208 of the adjacent two units are opposed to each other in the bending direction.
  • attachment members that employ other combinations of hooks and/or bend directions are also possible.
  • the stomach environment is acidic and the intestinal environment is alkaline.
  • a coating layer may be disposed on the outer side of the attachment member or wrapped around the attachment member, and before the coating layer is degraded, the capsule may be To advance smoothly along the digestive tract (esophagus, stomach, intestines, etc.).
  • the coating may be enteric, which does not degrade in the stomach and degrades in the intestine to ensure that the attachment components are exposed in the intestinal tract, thereby allowing the capsule to effectively adhere to the intestinal wall.
  • the coating may be gastric soluble, which degrades in the stomach to ensure that the attachment components are exposed in the stomach, thereby allowing the capsule to effectively adhere to the stomach wall.
  • FIG. 3 shows a perspective view of the appearance of a capsule 300 of one embodiment.
  • the appearance of the capsule 300 generally appears as an oblong or olive shape.
  • the attachment member 310 composed of the viscous body 308 is disposed on one side of the outer surface of the capsule.
  • the viscous body 308 adheres to the tissue of the stomach wall or the intestinal wall to effectively attach the capsule 300 to the stomach wall or the intestinal wall.
  • a coating layer may also be disposed outside the attachment member 310, and the capsule 300 can smoothly advance along the digestive tract (esophagus, stomach, intestine, etc.) before the coating is degraded.
  • the coating may be enteric to ensure that the attachment member 310 is exposed in the intestine such that the capsule 300 is effectively attached to the intestinal wall.
  • the coating may be gastric soluble, which degrades in the stomach to ensure that the attachment member 310 is exposed in the stomach, thereby allowing the capsule 300 to effectively adhere to the stomach wall.
  • the appearance of the capsule is generally spherical.
  • the outer shell of the capsule can be made from a variety of biocompatible polymers known in the art, such as various biodegradable polymers.
  • 4A illustrates an outer casing 402 in one embodiment of the present invention that is integrally formed of a biodegradable material and has grooves or depressions 404 on its outer surface such that the outer shell first degrades in the grooves or depressions.
  • An outer panel 403 of optional size and shape as shown in Figure 4B is created to facilitate passage of the capsule through the gastrointestinal tract and to reduce the likelihood of the capsule being stuck within the gastrointestinal tract.
  • FIG. 5A shows a schematic cross-sectional view of a capsule 500 of one embodiment.
  • the outer casing 502 generally assumes an oblong or olive shape.
  • An attachment member 510 composed of a plurality of hooks 508 is disposed on one side of the outer surface of the outer casing 502.
  • the hook 508 can engage the tissue of the stomach wall or the intestinal wall to effectively attach the capsule 500 to the stomach wall or the intestinal wall.
  • a needle 520, a support 524, and a sachet 528 are disposed on a side close to the attachment member 510, and an expansion member 530 is disposed on a side away from the attachment member 510.
  • the needle 520 and the support 524 are integrally connected, generally located adjacent to the attachment member 510 with the needle tip facing the outside of the capsule 500.
  • the needle 520 is hollow with an infusion line 521 in communication with a conduit 525 in the holder 524.
  • a drug such as a liquid is stored in the sachet 528.
  • the sachet 528 is sealingly coupled to the support 524 and exposes the end opening 526 of the conduit 525 inside the sachet such that the chamber within the sachet is in fluid communication with the infusion conduit 521.
  • the sachet 528 is relatively soft and easily deformed, and the needle 520 and the support 524 are relatively strong and are not easily deformed.
  • the outer casing 502 is provided with at least one opening 506 on one side of the expansion element 530.
  • the expansion member 530 contacts the body fluid through the opening 506 in the stomach or intestine to cause volume expansion.
  • the material contained in the expansion element 530 is, for example but not limited to, a superabsorbent polymer (SAP), such as the BASF Corporation. Series SAP. Due to the limitations of the outer casing 502, the expansion element 530 will squeeze the needle 520, the support 524 and the sachet 528 toward the attachment member 510 side. The needle 520 thus penetrates the outer casing 502 and penetrates the stomach wall or intestinal wall tissue to which the attachment element 510 is attached. The sachet 528 is deformed by extrusion so that the stored drug solution is injected into the stomach wall or the intestinal wall tissue via the infusion tube 521.
  • a coating layer 512 may be disposed outside the attachment member 510 or enclosing the attachment member 510, and the capsule 500 may smoothly advance along the digestive tract (esophagus, stomach, intestine, etc.) before the coating layer 512 is degraded.
  • the opening 506 can be obscured by the obscuring layer 516 such that the expansion element 530 does not contact body fluids in the stomach or intestine until the capsule 500 reaches the desired site of administration.
  • the coating layer 512 and the shielding layer 516 may both be enteric, and the degradation speed of the coating layer 512 is faster than the degradation speed of the shielding layer 516; after the coating layer 512 degrades and exposes the attachment member 510 and adheres to the intestinal wall, The obscuring layer 516 at the opening 506 degrades and exposes the expansion element 530.
  • the coating layer 512 and the shielding layer 516 may both be gastric-soluble, and the degradation speed of the coating layer 512 is faster than the degradation speed of the shielding layer 516; after the coating layer 512 degrades and exposes the attachment member 510 and adheres to the stomach wall, the opening 506 The obscuring layer 516 at the site degrades and exposes the expansion element 530.
  • Fig. 5B is a cross-sectional view showing the capsule 500' of a variation of the embodiment shown in Fig. 5A.
  • the difference from the capsule 500 includes that at least one conduit 525' is provided with a plurality of openings 526' on the support 524', which helps to reduce the deformed sachet 528' blocking the opening 526' and causing the remaining liquid medicine The risk of injecting into the stomach wall or intestinal wall tissue through the conduit 525' and the infusion conduit 521' cannot continue.
  • Figure 6 shows a schematic cross-sectional view of a capsule 600 of one embodiment.
  • the outer casing 602 generally assumes an oblong or olive shape.
  • An attachment member 610 composed of a plurality of hooks 608 is disposed on one side of the outer surface of the outer casing 602.
  • the hook 608 can engage the tissue of the stomach wall or the intestinal wall to effectively attach the capsule 600 to the stomach wall or the intestinal wall.
  • a needle 620, a support 624, and a sachet 628 are disposed on a side close to the attachment member 610, and a side away from the attachment member 610 is provided.
  • An expansion element 630 is placed.
  • the needle 520 and the support 524 are integrally connected, generally located adjacent to the attachment member 610 with the needle tip facing the outside of the capsule 600.
  • the needle 620 is hollow, with the infusion conduit 621 communicating with the conduit 625 in the holder 624.
  • a drug such as a liquid is stored in the sachet 628.
  • the sachet 628 is sealingly coupled to the holder 624 and exposes the end opening 626 of the conduit 625 inside the sachet such that the chamber within the sachet is in fluid communication with the infusion conduit 621.
  • the sachet 628 is relatively soft and easily deformed, and the needle 620 and the support 624 are relatively strong and are not easily deformed.
  • the outer casing 602 is provided with at least one opening 606 on one side of the expansion element 630.
  • the expansion element 630 includes a bladder 632 and a valve 634.
  • valve 634 clamps the middle of bladder 632 to form two first chambers 635 and a second chamber 637 that are isolated from one another, storing first reactants and second reactants, respectively.
  • the valve 634 is degraded by contact with the body fluid through the opening 606, and the first chamber 635 and the second chamber 637 are in communication with each other, and the first reactant and the second reactant are mutually connected to each other. Mixing occurs chemically and/or physically to cause volume expansion.
  • the first reactant and the second reactant are mixed to produce carbon dioxide, resulting in volume expansion. Due to the limitations of the outer casing 602, the expanded bladder 632 will squeeze the needle 620, the support 624, and the sachet 628 toward the side of the attachment member 610. The needle 620 thus penetrates the outer casing 602 and penetrates the stomach wall or intestinal wall tissue to which the attachment element 610 is attached. The sachet 628 is deformed by extrusion so that the stored medical solution is injected into the stomach wall or intestinal wall tissue via the infusion conduit 621.
  • the expanded bladder 632 will squeeze the needle 620, the support 624, and the sachet 628 toward the side of the attachment member 610.
  • the needle 620 thus penetrates the outer casing 602 and penetrates the stomach wall or intestinal wall tissue to which the attachment element 610 is attached.
  • the sachet 628 is deformed by extrusion so that the stored medical solution is injected into the stomach wall or intestinal wall tissue via the infusion conduit 621.
  • a coating layer may be disposed outside the attachment member 610 or enclosing the attachment member 610, and the capsule 600 may smoothly advance along the digestive tract (esophagus, stomach, intestine, etc.) before the coating is degraded.
  • the opening 606 can be obscured by the obscuring layer such that the valve 634 does not contact body fluids in the stomach or intestine until the capsule 600 reaches the desired site of administration.
  • the coating layer and the shielding layer may both be enteric, and the degradation rate of the coating layer is faster than the degradation speed of the shielding layer; after the coating layer degrades and exposes the attachment member 610 and adheres to the intestinal wall, the opening 606
  • the masking layer degrades and exposes valve 634.
  • the coating layer and the shielding layer may both be gastric-soluble, and the degradation rate of the coating layer is faster than the degradation rate of the shielding layer; when the coating layer degrades and exposes the attachment member 610 and adheres to the stomach wall, the shielding layer at the opening 606 Degradation and exposure of valve 634.
  • FIG. 7 shows a cross-sectional view of a capsule 700 of one embodiment.
  • the outer casing 702 generally assumes an oblong or olive shape.
  • An attachment member 710 composed of a plurality of hooks 708 is disposed on one side of the outer surface of the outer casing 702.
  • the hook 708 can bite the tissue of the stomach wall or the intestinal wall to effectively attach the capsule 700 to the stomach wall or the intestinal wall.
  • a needle-shaped body 720 and a support 724 are provided on a side close to the attachment member 710, and an expansion member 730 is provided on a side away from the attachment member 710.
  • the support 724 holds the needle 720, generally adjacent to the attachment member 710, with the needle tip 720 facing the outside of the capsule 700.
  • a coating may also be provided on the outside of the attachment member 710 or wrapped around the attachment member 710, and the capsule 700 may smoothly advance along the digestive tract (esophagus, stomach, intestine, etc.) before the coating is degraded.
  • the opening 706 can be obscured by the obscuring layer such that the expansion element 730 does not contact body fluids in the stomach or intestine until the capsule 700 reaches the desired site of administration.
  • the coating layer and the shielding layer may both be enteric, and the degradation rate of the coating layer is faster than the degradation speed of the shielding layer; when the coating layer degrades and exposes the attachment member 710 and adheres to the intestinal wall, the opening 706 The masking layer degrades and exposes the expansion element 730.
  • the coating layer and the shielding layer may both be gastric-soluble, and the degradation rate of the coating layer is faster than the degradation rate of the shielding layer; when the coating layer degrades and exposes the attachment member 710 and adheres to the stomach wall, the shielding layer at the opening 706 The expansion element 730 is degraded and exposed.
  • FIG. 8 shows a schematic cross-sectional view of a capsule 800 of one embodiment.
  • the outer casing 802 generally assumes an oblong or olive shape.
  • An attachment member 810 including a viscous body is disposed on one side of the outer surface of the outer casing 802.
  • the capsule 800 can be effectively attached to the stomach wall or the intestinal wall by stickiness.
  • a needle-like body 820 and a support 824 are provided on a side close to the attachment member 810, and an expansion member 830 is provided on a side away from the attachment member 810.
  • the support 824 holds the needle 820, generally adjacent to the attachment member 810, with the needle tip 820 facing the outside of the capsule 800.
  • the needle 820 contains a solid drug and is provided with a barb 821.
  • the outer casing 802 is provided with at least one opening 806 on one side of the expansion element 830.
  • the expansion element 830 includes a bladder 832 and a valve 834. For example but not Limited to the valve 834 clamping the middle of the bladder 832, forming two first chambers 835 and a second chamber 837 that are isolated from one another, storing the first reactant and the second reactant, respectively.
  • the valve 834 When the capsule 800 is attached to the stomach or intestine by the attachment member 810, the valve 834 is degraded by contact with the body fluid through the opening 806, and the first chamber 835 and the second chamber 837 are in communication with each other, the first reactant and the second reactant are mutually connected to each other. Mixing occurs chemically and/or physically to cause volume expansion.
  • the first reactant and the second reactant such as but not limited to, acetic acid and sodium bicarbonate, respectively, are mixed to produce carbon dioxide, resulting in volume expansion. Due to the limitations of the outer casing 802, the expanded bladder 832 will squeeze the support 824 and the needle 820 toward the side of the attachment member 810.
  • the needle 820 thus penetrates the outer casing 802 and penetrates the stomach wall or intestinal wall tissue to which the attachment element 810 is attached, and the barb 821 causes the needle 820 to remain inside the tissue. Thereafter, the needle 820 is degraded inside the tissue to complete the administration.
  • a coating layer may also be disposed on the outside of the attachment member 810, and the capsule 800 can smoothly advance along the digestive tract (esophagus, stomach, intestine, etc.) before the coating is degraded.
  • the opening 806 can be obscured by the obscuring layer such that the valve 834 does not contact body fluids in the stomach or intestine until the capsule 800 reaches the desired site of administration.
  • the coating layer and the shielding layer may both be enteric, and the degradation rate of the coating layer is faster than the degradation speed of the shielding layer; when the coating layer degrades and exposes the attachment member 810 and adheres to the intestinal wall, the opening 806 The masking layer degrades and exposes valve 834.
  • the coating layer and the shielding layer may both be gastric-soluble, and the degradation rate of the coating layer is faster than the degradation rate of the shielding layer; when the coating layer degrades and exposes the attachment member 810 and adheres to the stomach wall, the shielding layer at the opening 806 Degrading and exposing valve 834.
  • the support 924 holds the needle 920 substantially in the immediate vicinity of the attachment member 910 with the needle tip 920 facing the outside of the capsule 900.
  • the needle 920 contains a solid drug and is provided with a barb 921.
  • Each of the actuating members 930 includes an elastic member (e.g., a spring) 933 and a limit member 935 between the respective holder 924 and the other side of the outer casing 902. In the initial state, the limiting member 935 will support the attachment member 924 with the housing 902 and the attachment member 910. The opposite side is joined together such that the spring 933 is in a compressed state. At least one opening 906 is provided on the outer casing 902 adjacent to the limiting member 935.
  • a coating layer 912 may also be disposed outside the attachment member 910 or enclosing the attachment member 910.
  • the capsule 900 may smoothly advance along the digestive tract (esophagus, stomach, intestines, etc.) before the coating 912 degrades.
  • the opening 906 can be obscured by the obscuring layer 916 such that the stop element 935 does not contact body fluids in the stomach or intestine until the capsule 900 reaches the desired site of administration.
  • the coating layer 912 and the shielding layer 916 may both be enteric, and the degradation speed of the coating layer 912 is faster than the degradation speed of the shielding layer 916; after the coating layer 912 degrades and exposes the attachment member 910 and adheres to the intestinal wall, The obscuring layer 916 at the opening 906 degrades and exposes the stop element 935.
  • the coating layer 912 and the shielding layer 916 may both be gastric-soluble, and the degradation speed of the coating layer 912 is faster than the degradation speed of the shielding layer 916; after the coating layer 912 degrades and exposes the attachment member 910 and adheres to the stomach wall, the opening 906 The obscuring layer 916 at the location degrades and exposes the stop element 935.
  • the coating layer 912, the shielding layer 916, and the limiting element 935 comprise materials such as, but not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), acrylic resin, polyvinylpyrrolidone (PVP). , methacrylic acid-ethyl acrylate copolymer or a mixture thereof.
  • HPMC hydroxypropyl methylcellulose
  • HPC hydroxypropyl methylcellulose
  • HPC hydroxypropyl cellulose
  • acrylic resin acrylic resin
  • PVP polyvinylpyrrolidone
  • methacrylic acid-ethyl acrylate copolymer or a mixture thereof.
  • Figure 9B shows a schematic cross-sectional view of a capsule 900' of one embodiment.
  • the main difference of the capsule 900' compared to the capsule 900 includes that the stop member 935' is located between the holder 924' and the outer casing on the side of the attachment member 910'. In the initial state, the stopper member 935' supports the holder 924' such that the spring 933' is in a compressed state. At least one opening 906' is provided on the outer casing 902' adjacent to the limiting member 935'.
  • the body fluid entering the housing 902' through the opening 906' causes the stop member 935' to degrade, the support 924' and the needle 920' will be at the spring 933'
  • the restoring force urges the lower attachment member 910' to be pressed.
  • the needle 920' thus penetrates the outer casing 902' and penetrates the stomach wall or intestinal wall tissue to which the attachment member 910' is attached, the barb 921'
  • the needle 920' remains inside the tissue. Thereafter, the needle 920' is degraded inside the tissue to complete the administration.
  • the coating layer 912', the shielding layer 916', and the limiting element 935' comprise materials such as, but not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), acrylic resin, polyvinylpyrrolidone. (PVP), methacrylic acid-ethyl acrylate copolymer or a mixture thereof.
  • HPMC hydroxypropyl methylcellulose
  • HPC hydroxypropyl methylcellulose
  • HPC hydroxypropyl cellulose
  • acrylic resin acrylic resin
  • PVP polyvinylpyrrolidone.
  • methacrylic acid-ethyl acrylate copolymer or a mixture thereof.
  • the outer edge of the skirt 1027 abuts the inner surface of the outer casing 1002.
  • An elastic member (spring) 1033 and a stopper member 1035 are disposed between the holder 1024 and the side of the outer casing 1002 away from the attachment member 1010. In the initial state, the limiting member 1035 will support the attached component of the housing 1024 and the housing 1002. The opposite sides of 1010 are joined together such that spring 1033 is in a compressed state. At least one opening 1006 is provided on the outer casing 1002 near the limiting member 1035.
  • the body fluid entering the outer casing 1002 through the opening 1006 causes the stopper member 1035 to degrade, and the spring 1033 presses the needle 1020 toward the attachment member 1010 under the restoring force. 1024 and sachet 1028.
  • the needle 1020 thus penetrates the outer casing 1002 and penetrates the stomach wall or intestinal wall tissue to which the attachment element 1010 is attached.
  • the sachet 1028 is deformed by extrusion such that the stored medical fluid is injected into the stomach wall or intestinal wall tissue via the infusion conduit 1021.
  • the coating layer 1012 and the shielding layer 1016 may both be enteric, and the degradation rate of the coating layer 1012 is faster than the degradation rate of the shielding layer 1016; after the coating layer 1012 degrades and exposes the attachment member 1010 and adheres to the intestinal wall, The masking layer 1016 at the opening 1006 degrades and exposes the stop element 1035.
  • the coating layer 1012 and the shielding layer 1016 may all be gastric-soluble, and the degradation speed of the coating layer 1012 is faster than the degradation speed of the shielding layer 1016; after the coating layer 1012 degrades and exposes the attachment member 1010 and adheres to the stomach wall, the opening 1006
  • the obscuring layer 1016 at the site degrades and exposes the expansion element 1030.
  • a needle 1120, a support 1124, a sachet 1128 are disposed on a side close to the attachment member 1110, and a needle 1170, a support 1174, a sachet 1178, and a support 1124 and 1174 are disposed on a side close to the attachment member 1160.
  • An expansion element 1130 is provided therebetween.
  • the needle 1120 and the support 1124 are integrally connected, generally adjacent to the attachment member 1110, with the tip direction facing the outside of the capsule 1100.
  • the needle 1120 is hollow, with the infusion conduit 1121 communicating with the conduit 1125 in the holder 1124.
  • a drug such as a liquid is stored in the sachet 1128.
  • the sachet 1128 is sealingly coupled to the support 1124 and exposes the end opening 1126 of the conduit 1125 inside the sachet such that the chamber within the sachet is in fluid communication with the infusion conduit 1121.
  • the sachet 1128 is relatively soft and easily deformed, and the needle 1120 and the support 1124 are relatively strong and not easily deformable.
  • the needle 1170, the support 1174, and the sachet 1178 are generally disposed similarly to the needle 1120, the support 1124, and the sachet 1128. At least one opening is provided on the outer casing 1102 proximate the expansion element 1130.
  • the expansion element 1130 contacts the body fluid through the opening in the stomach or intestine to cause volume expansion.
  • the material contained in the expansion element 1130 is, for example but not limited to, a superabsorbent polymer (SAP), such as the BASF Corporation. Series SAP.
  • SAP superabsorbent polymer
  • the expansion element 1130 will press the needle 1120, the holder 1124, and the sachet 1128 toward the attachment member 1110 side, and press the needle 1170, the holder 1174, and the sachet 1178 toward the attachment member 1160 side.
  • the needles 1120, 1170 thus penetrate the outer casing 1102 and penetrate the stomach wall or intestinal wall tissue to which the attachment elements 1110, 1160 are attached.
  • the sachets 1128, 1178 are deformed by extrusion such that the stored medical fluid is injected into the stomach wall or intestinal wall tissue via the infusion conduits 1121, 1171.
  • the coating layers 1112 and 1162 may also be disposed outside the attachment members 1110 and 1160, or around the attachment members 1110 and 1160, and the capsule 1100 may smoothly follow the digestive tract (esophagus, stomach, etc.) before the coating layers 1112 and 1162 are degraded. Intestines, etc.) Advance.
  • the opening adjacent the expansion element 1130 can be obscured by the obscuring layer such that the expansion element 1130 does not contact body fluids in the stomach or intestine until the capsule 1100 reaches the desired site of administration.
  • the cladding layers 1112, 1162 and the shielding layer may both be enteric, and the degradation speed of the coating layers 1112 and 1162 is faster than the degradation speed of the shielding layer; when the coating layers 1112, 1162 are degraded to expose the adhesion members 1110, 1160 and adhered After the intestinal wall, the obscuring layer at the opening degrades and exposes the expansion element 1130.
  • the cladding layers 1112, 1162 and the shielding layer may all be gastric-soluble, and the degradation speed of the coating layers 1112 and 1162 is faster than the degradation speed of the shielding layer; when the coating layers 1112 and 1162 degrade and expose the adhesion members 1110 and 1160 and adhere thereto After the stomach wall, the masking layer at the opening degrades and exposes the expansion element 1130.
  • a needle-like body 1220 and a support 1224 are disposed on a side close to the attachment member 1210, and a needle-like body 1270 and a support 1274 are disposed on a side close to the attachment member 1260, and a support is provided between the holders 1224 and 1274.
  • the support 1224 holds the needle 1220 substantially in the immediate vicinity of the attachment member 1210 with the needle tip 1220 facing the outside of the capsule 1200.
  • the support 1274 holds the needle 1270 substantially in the immediate vicinity of the attachment member 1260 with the needle tip 1270 facing the outside of the capsule 1200.
  • the needles 1220, 1270 contain solid drugs and are provided with barbs 1221, 1271, respectively.
  • At least one opening 1206 is provided on the outer casing 1202 adjacent the expansion element 1230.
  • the expansion element 1230 contacts the body fluid through the opening 1206 in the stomach or intestine causing volume expansion.
  • the expansion member 1230 presses the needle body 1220 and the holder 1224 toward the attachment member 1110 side, and presses the needle body 1270 and the holder 1274 toward the attachment member 1260 side.
  • the material contained in the expansion element 1230 is, for example but not limited to, a superabsorbent polymer (SAP), such as the BASF Corporation. Series SAP.
  • the needles 1220, 1270 thus penetrate the outer casing 1202 and penetrate the stomach wall or intestinal wall tissue to which the attachment elements 1210, 1260 are attached, and the barbs 1221, 1271 maintain the needles 1220, 1270 inside the tissue. Thereafter, the needles 1220, 1270 are degraded inside the tissue to complete the administration.
  • Cladding layers 1212, 1262 may also be provided on the outside of the attachment members 1210, 1260 or around the attachment members 1210, 1260. Prior to degradation of the coating 1212, 1262, the capsule 1200 can smoothly advance along the digestive tract (esophagus, stomach, intestines, etc.). The opening 1206 can be obscured by the obscuring layer 1216 such that the expansion element 1230 does not contact body fluids in the stomach or intestine until the capsule 1200 reaches the desired site of administration.
  • the cladding layers 1212, 1262 and the shielding layer 1216 may all be enteric, and the degradation speed of the coating layers 1212, 1262 is faster than the degradation speed of the shielding layer 1216; when the coating layers 1212, 1262 degrade the exposed components 1210, 1260 After being attached to the intestinal wall, the obscuring layer 1216 at the opening 1206 degrades and exposes the expansion element 1230.
  • the coating layers 1212, 1262 and the shielding layer 1216 may all be gastric-soluble, and the degradation speed of the coating layers 1212, 1262 is faster than the degradation speed of the shielding layer 1216; when the coating layers 1212, 1262 are degraded to expose the attachment members 1210, 1260 After being attached to the stomach wall, the shielding layer 1216 at the opening 1206 degrades and exposes the swelling element.
  • the coatings 1212, 1262 and the shielding layer 1216 comprise materials such as, but not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), acrylic resin, polyvinylpyrrolidone (PVP), methyl Acrylic acid-ethyl acrylate copolymer or a mixture thereof.

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Abstract

L'invention porte sur un dispositif ingérable (100, 200, 300, 500, 500', 600, 700, 800, 900, 900', 1000, 1100, 1200), comprenant un boîtier (402, 502, 602, 702, 802, 902, 902', 1002, 1102, 1202) ; une ou plusieurs parties de pénétration (520, 620, 720, 820, 920, 920', 1020, 1120, 1170, 1220, 1270) ; des pièces d'actionnement (530, 630, 730, 830, 930, 933', 1030, 1130, 1230) ; des parties de fixation (108, 210, 310, 510, 610, 710, 810, 910, 910', 1010, 1110, 1160, 1210, 1260) situées au niveau de la surface externe du boîtier (402, 502, 602, 702, 802, 902, 902', 1002, 1102, 1202) ; et un médicament situé à l'intérieur du boitier (402, 502, 602, 702, 802, 902, 902', 1002, 1102, 1202).
PCT/CN2016/078405 2015-04-02 2016-04-01 Dispositif ingérable WO2016155671A1 (fr)

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CN201510155518.7 2015-04-02

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WO2019222572A1 (fr) 2018-05-17 2019-11-21 Massachusetts Institute Of Technology Capsules à libération rapide
US11179341B2 (en) 2017-05-17 2021-11-23 Massachusetts Institute Of Technology Self-righting articles
US11202903B2 (en) 2018-05-17 2021-12-21 Massachusetts Institute Of Technology Systems for electrical stimulation
EP3880177A4 (fr) * 2018-11-15 2022-10-12 Massachusetts Institute of Technology Composants d'actionnement et procédés associés
US11541016B2 (en) 2017-05-17 2023-01-03 Massachusetts Institute Of Technology Self-righting systems, methods, and related components
US11541216B2 (en) 2019-11-21 2023-01-03 Massachusetts Institute Of Technology Methods for manufacturing tissue interfacing components
US11771829B2 (en) 2019-02-01 2023-10-03 Massachusetts Institute Of Technology Systems and methods for liquid injection

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