Drug delivery device in human body

Abstract

The invention discloses a drug delivery device in a human body cavity, which comprises an inflatable balloon, at least one part of the outer wall of the balloon is provided with a protective shell, the balloon is provided with an inner cavity, and the protective shell can be dissolved by specific body fluid in the human body cavity; the triggering part is arranged in an inner cavity of the balloon, and the triggering part can react with body fluid to generate fluid to inflate the balloon when making contact with the body fluid, so that the inflated balloon is tightly attached to the wall of a body cavity; the propelling part is arranged in the inner cavity of the balloon and comprises a tissue penetrating component, and the triggering part can generate power to propel the tissue penetrating component; and the containing part is used for containing a medicine preparation, and the triggering part can push and press the liquid medicine preparation contained in the containing part into the pushing part after the balloon is inflated, and injects the liquid medicine preparation into the inner wall tissue of the human body cavity through the tissue penetrating component. By means of the device, macromolecular drugs or preparations can be injected into the inner wall of the human body cavity, such as the tissue of the intestinal wall.

Description

[0001] This application is a divisional application of invention patent 202411306766.2. TECHNICAL FIELD

[0002] The present application relates to a drug delivery device, in particular a drug delivery device capable of injecting macromolecular drugs or preparations into the tissue of the inner wall of the natural cavity in the human body. BACKGROUND

[0003] With the development of biotechnology, more and more biological preparations based on oligonucleotides, proteins, polypeptides and other macromolecules have emerged, and the drug delivery route is a common problem encountered in the clinical application of biological preparations. Because biological preparations are easily degraded in the liver and gastrointestinal tract when taken orally, reducing the effective bioavailability of biological preparations; when injected, it is difficult to maintain stable blood drug concentration in the body, and frequent injection also causes great inconvenience and pain to the recipients, and they also face the situation of no available drugs for intravenous intolerant patients; transdermal drug delivery is also restricted by the large molecular weight of biological preparations, and it is difficult to penetrate through the stratum corneum of the skin into the human circulatory system. Therefore, small intestinal wall injection of macromolecular preparations in the natural cavity in the body as an innovative drug delivery method in addition to conventional oral, parenteral injection and transdermal drug delivery will create a new drug delivery method.

[0004] Compared with ordinary drug delivery methods, the following advantages of intracavity wall injection drug delivery are obtained:

[0005] (1) Solving the problem of no available drugs for intravenous intolerant patients, avoiding various adverse reactions of intravenous infusion.

[0006] (2) Effectively avoiding the liver "first pass effect" and gastrointestinal inactivation that may occur when taking drugs orally, improving bioavailability and treatment effect.

[0007] (3) Providing a mild drug delivery method to improve the experience of the recipients.

[0008] (4) Avoiding the fear of frequent injections of recipients, effectively improving the compliance of recipients. SUMMARY

[0009] The technical problem to be solved by the present application is to provide a drug delivery device capable of directly injecting drugs into the tissue of the inner wall of the natural cavity in the human body.

[0010] To this end, the present application provides a drug delivery device for injection into the inner wall of a human body cavity, comprising: an inflatable balloon, at least a portion of the outer wall of the balloon being provided with a protective shell, the balloon having an inner cavity, the protective shell being capable of being dissolved by body fluid in the human body; a trigger portion provided in the inner cavity of the balloon, the trigger portion being capable of generating fluid to inflate the balloon when in contact with the body fluid, so that the inflated balloon is tightly attached to the wall of the body cavity; a propulsion portion in the inner cavity of the balloon, the propulsion portion comprising a tissue-penetrating member, the trigger portion being capable of generating power to propel the tissue-penetrating member; and a containing portion for containing a drug preparation, wherein the trigger portion is capable of pushing the liquid drug preparation contained in the containing portion into the propulsion portion after the balloon is inflated, and injecting the liquid drug preparation into the human tissue through the tissue-penetrating member.

[0011] Preferably, the drug delivery device further comprises a limiting element provided on the outer surface of the balloon, the limiting element being used to control the inflation deformation of the balloon.

[0012] Preferably, the limiting element is a shaped stent, the shaped stent being fixed on a portion of the outer surface of the balloon, so that the portion of the balloon in the gap between the shaped stents allows inflation deformation, while the portion of the balloon on which the shaped stent is fixed is attached to the body wall and the injection position of the drug preparation is in this portion.

[0013] Preferably, the trigger portion comprises a trigger cabin and a trigger mechanism provided in the trigger cabin, and a pushing member triggered by the trigger mechanism.

[0014] Preferably, the trigger mechanism comprises a messenger, after the protective shell is dissolved, the messenger contacts the body fluid to react to release gas to inflate the balloon.

[0015] Preferably, the pushing member is a pushing piston, the pushing piston is capable of moving at an angle along the balloon, preferably longitudinally, but before the messenger reacts, the pushing piston is fixed by the messenger, after the messenger reacts, the pushing piston is released.

[0016] Preferably, the messenger and the pushing piston are kept in a locked state by a form fit.

[0017] Preferably, the trigger mechanism further comprises an actuating mechanism provided between the wall of the trigger cabin and the pushing assembly, in the initial state, the actuating mechanism is in an inactive state, i.e. a locked state, after the trigger mechanism is activated, the actuating mechanism is activated to cause the pushing member to move to generate pressure on the containing portion.

[0018] Preferably, the messenger is made of a material that can react with water.

[0019] Preferably, the actuating mechanism is a compression spring, or other mechanism capable of generating pressure such as a compressed gas bladder.

[0020] Preferably, the propulsion unit comprises a propulsion mechanism having a propulsion piston, the tissue-penetrating member being fixedly mounted on the propulsion piston, in the initial state, the tissue-penetrating member being housed in the propulsion chamber, in the working state, the propulsion piston and the tissue-penetrating member being pushed out together, the tissue-penetrating member puncturing the balloon, allowing the liquid drug formulation to be injected into the tissue of the inner wall of the body cavity via the tissue-penetrating member.

[0021] Preferably, the propulsion piston and the tissue-penetrating member are pushed out under the pressure of the drug formulation.

[0022] Preferably, the propulsion mechanism further comprises a homing assembly, when the injection is completed, the homing assembly homing the propulsion piston and retracting the tissue-penetrating member into the propulsion chamber.

[0023] Preferably, the homing assembly is a tension spring fixed between the propulsion piston and the wall of the propulsion chamber, or a mechanism capable of generating pressure.

[0024] Preferably, the propulsion piston moves in a direction that is at an angle to the longitudinal direction of the balloon, so that the direction of movement of the tissue-penetrating member is at an angle to the longitudinal direction.

[0025] Preferably, the angle between the direction of movement of the tissue-penetrating member and the longitudinal direction is 45° to 135°.

[0026] Preferably, the drug delivery device further comprises a sensing assembly arranged near the propulsion chamber, for sensing the position of the propulsion piston and / or the tissue-penetrating member, to confirm that the tissue-penetrating member is homed to a safe position.

[0027] Preferably, the sensing assembly comprises a sensor, and a sensing marker is arranged on the propulsion piston and / or the tissue-penetrating member, the sensing assembly being configured to detect whether the sensing marker reaches a threshold value, to confirm the position of the propulsion piston.

[0028] Preferably, the sensing marker comprises a magnetic material, and the sensing assembly is configured to detect the magnetic flux.

[0029] Preferably, the body fluid is small intestinal fluid.

[0030] Preferably, the tissue-penetrating member is an injection component.

[0031] Preferably, the injection component is made of a degradable material.

[0032] The present application has the following beneficial effects.

[0033] 1. The delivery device of the present application can be used to directly inject a drug into the body, thereby avoiding the adverse effects of intravenous injection.

[0034] 2. The delivery device of the present application can ensure that the drug is reliably injected into the intestinal wall.

[0035] 3. The delivery device of the present application can ensure that the injection component is retracted after injection is completed, thereby avoiding personal injury.

[0036] 4. The present application also includes a sensing portion to detect the position of the injection component and confirm whether the injection component is retracted. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 is a schematic view of the drug delivery device of the present application.

[0038] Figure 2 is a schematic view of the drug delivery device located in a cavity (e.g., the small intestine).

[0039] Figure 3 is a schematic view of the drug delivery device after the protective shell is decomposed and the balloon begins to inflate after the drug delivery device contacts the small intestinal fluid.

[0040] Figure 4 is a schematic view of the drug delivery device during injection.

[0041] Figure 5 is a schematic view of the drug delivery device after injection is completed and the injection component is activated to retract.

[0042] Figure 6 is a schematic view of the drug delivery device after the injection component is fully homed.

[0043] Figure 7 is a schematic view of the drug delivery device after the capsule is deflated and the drug delivery device is expelled from the body.

[0044] For the sake of clarity, the same reference numbers will be used in different drawings to refer to the same or like elements incorporated in the drawings. It is contemplated that elements disclosed in one embodiment can be advantageously used in other embodiments without specific recitation. DETAILED DESCRIPTION

[0045] Referring to Figure 1 , the drug delivery device of the present application has a shape similar to a capsule or pill, and thus can also be referred to as a delivery capsule or simply a capsule.

[0046] As Figure 1As shown, the delivery capsule according to the present application comprises a balloon 1, at least a portion of the outer wall of the balloon 1 is provided with a protective shell 10. In the present embodiment, the protective shell 10 is an enteric shell, so that the delivery capsule is not affected in the stomach after entering the human body, and enters the intestinal tract 7 of the human body, for example the small intestine, and starts to act after contacting the small intestinal fluid. However, the protective shell 10 can also be made of a material that dissolves or degrades in other digestive tracts or body cavities, and the present application does not make any limitation.

[0047] The balloon 1 is made of a material that can be stretched during and / or after inflation. The balloon 1 is provided with a structure for controlling the balloon to deform and expand. The structure for controlling the balloon to deform and expand can be a rigid limiting element, in the present embodiment, the limiting element is a shaping stent 2, which is clamped on a portion of the outer surface of the balloon 1, and this portion of the outer surface is constrained by the shaping stent 2 and cannot deform freely. The remaining portion of the balloon 1 that is not constrained by the shaping stent 2 can freely expand and deform in the gap of the shaping stent 2 under the action of the gas pressure inside the balloon. When the balloon expands, the portion of the balloon on which the shaping stent 2 is fixed can be attached to the body wall, and the injection site (especially the injection hole) of the drug preparation is in this portion. From Figure 1 It can be seen that the shaping stent 2 is arranged on the upper half of the balloon 1. When the balloon 1 is inflated, the lower half of the balloon 1 can abut against the intestinal wall and push the portion provided with the shaping stent 2 to abut against the intestinal wall, so that the position where the drug preparation is to be injected, i.e. the injection hole 12, can reliably contact the intestinal wall (see Figure 3 ).

[0048] The balloon 1 has an inner cavity, in which a trigger portion, a propulsion portion and a containing portion are arranged. The trigger portion can react with the body fluid when it contacts the body fluid, generate a fluid to inflate the balloon, so that the inflated balloon is attached to the body cavity wall. The propulsion portion includes a tissue-penetrating member, and the trigger portion can generate power to propel the tissue-penetrating member. The containing portion is used to contain the fluid drug preparation.

[0049] The trigger portion pushes the fluid drug preparation contained in the containing portion into the propulsion cabin 4 after the balloon is inflated, and injects the liquid drug preparation into the human body through the tissue-penetrating member.

[0050] In the present embodiment, the trigger portion is a trigger cabin 3 arranged on the first side (left side in the figure) in the longitudinal direction (or axial direction) of the inner cavity; the propulsion portion includes a propulsion cabin 4 arranged on the second side (right side in the figure); the containing portion is arranged between the trigger cabin 3 and the propulsion cabin 4, and can also be referred to as a preparation cabin 5. The sensing portion 6 is arranged around (for example, on the inner side or the outer side, in the present embodiment, on the outer side) the propulsion cabin 4.

[0051] The trigger compartment 3 comprises a trigger mechanism 31 and a push member. In this embodiment, the push member is a push piston 32. The trigger mechanism 31 is capable of triggering after the protective shell 10 is dissolved and contacts the body fluid, and pushes the drug preparation contained in the preparation compartment 5 into the propulsion compartment 4, and causes the propulsion mechanism in the propulsion compartment 4 to inject the drug preparation into the human body.

[0052] In this embodiment, the trigger mechanism 31 comprises a delivery body 312 and an actuating mechanism 311.

[0053] The delivery body 312 is composed of a material that reacts with water, and is covered in the protective shell 10. When the protective shell 10 is dissolved, the delivery body 312 contacts the water in the body fluid, and releases a large amount of gas (such as carbon dioxide) and water. The gas enters the balloon 1 from the exhaust hole 313, causing the balloon to expand.

[0054] As shown in Figure 3 Due to the restriction of the shaped stent 2, the balloon 1 will expand to the gap of the shaped stent 2 (the lower part in the figure), and this expanded posture will push the delivery capsule to one side of the intestinal tract, and will make the injection hole 12 of the delivery capsule tightly adhere to the intestinal wall, and will prepare for the reliable penetration of the tissue penetration member (injection member) into the intestinal wall. The injection hole 12 is closed before being punctured by the injection member.

[0055] As the reaction of the delivery body 312 proceeds, the actuating mechanism 311 is activated to provide pressure to the push piston 32. More specifically, the actuating mechanism 311 is arranged between the trigger compartment wall and the push piston 32, and is in an inactivated state, i.e. a locked state. In the initial state, the push piston 32 is constrained by the delivery body 312, and when the delivery body 312 is dissolved by the reaction, the push piston 32 is released from the constraint, and the actuating mechanism 311 pushes the push piston 32 along the longitudinal direction towards the preparation compartment 5.

[0056] In this embodiment, the actuating mechanism 311 is a compression spring, which is biased in a compressed state in the initial state, and accumulates a biasing force. After the trigger mechanism 31 is triggered and the delivery body 312 is dissolved, the compression spring releases the biasing force, causing the push piston 32 to move along the balloon at an angle, preferably in the longitudinal direction, and push the preparation compartment 5. The actuating mechanism 311 can also be other elements, such as a water-reactive material that can quickly expand or a high-explosive material that can push the push piston 32 to move quickly in the longitudinal direction, or other mechanisms that can generate pressure such as a compressed air bag, and the present application is not limited thereto.

[0057] The transmitter 312 and the push piston 32 are shaped to fit together, holding the push piston 32 in place. As the transmitter 312 dissolves, it can no longer restrain the push piston 32, releasing it. In this embodiment, the front end of the transmitter 312 forms an umbrella-shaped barb 312a, which is embedded in the positioning hole 32a of the push piston 32. As the transmitter 312 dissolves, the umbrella-shaped barb 312a gradually disengages from the positioning hole 32a, thereby releasing the push piston 32. The transmitter 312 and the push piston can also be held together and locked together in other ways, releasing the push piston 32 after the transmitter 312 dissolves; this invention is not limited to these methods.

[0058] The formulation chamber 5 is used to contain liquid formulations. When the push piston 32 is pushed forward, the liquid formulations transmit pressure to the propulsion chamber 4.

[0059] The propulsion chamber 4 includes a propulsion mechanism and a return assembly 43. In this embodiment, the propulsion mechanism includes a propulsion piston 41 and a tissue penetration member, such as an injection component 42. The injection component 42 is mounted on the propulsion piston 41 and moves together with the propulsion piston 41 in a direction at an angle to the longitudinal direction, for example, within the range of 45° to 135°, preferably 90°. In the initial unactivated state, the injection component 42 is enclosed and housed inside the propulsion chamber.

[0060] like Figure 4 As shown, when the formulation chamber 5 is pressurized, the liquid drug formulation will transmit pressure to the propulsion chamber 4. Under pressure, the propulsion piston 41 moves outward, causing the injection component 42 to puncture the balloon 1 from the injection port of the delivery capsule. Since the injection port 12 of the delivery capsule is now close to the intestinal wall, the injection component 42 will pierce the intestinal wall and inject the formulation into the intestinal wall tissue. In this embodiment, the return component 43 is a tension spring fixed between the propulsion piston and the propulsion chamber wall. When the propulsion piston 41 moves outward, the tension spring is compressed.

[0061] like Figure 5 As shown, after injection, the pressure inside the formulation chamber 5 decreases due to the emptying of the formulation, and the outward thrust of the propulsion piston 41 also decreases. The return assembly 43 (i.e., the compressed tension spring) in the propulsion chamber 4 will cause the injection component 42 to withdraw from the intestinal wall tissue and begin to return to its original position and retract into the propulsion chamber 1. When the pressure inside the formulation chamber 5 is balanced with the external pressure, the return assembly 43 will cause the injection component 42 to return to a safe position within the delivery capsule propulsion chamber.

[0062] The return component 43 can also be made in a manner other than a tension spring. For example, magnetic components can be installed on the propulsion piston 41 and the propulsion chamber wall to create a repulsive force between them. After injection, this repulsive force can return the injection component 42 to its original position. Alternatively, the tension spring can be replaced by other restoring components with restoring force; this invention is not limited in this respect.

[0063] To confirm whether the injection member 42 is fully home, a sensing portion 6 is provided near the propulsion pod 4. In this embodiment, the sensing portion 6 is formed on the outside of the propulsion pod 4, i.e. the end of the capsule. However, the sensing portion 6 can also be formed on the inside of the propulsion pod 4 or at other locations, without limitation. The sensing portion 6 has a sensing assembly 61 mounted therein for sensing the home position of the push piston 32 in the propulsion pod 4 and the injection member 42 in the propulsion pod 4. In this embodiment, the sensing assembly 61 is a sensor having a sensing chip provided therein for sensing the position of the push piston 41. The push piston 41 has a sensing marker provided thereon.

[0064] In this embodiment, the push piston 41 is made of or comprises a magnetic material. When the sensing assembly 61 senses that the magnetic flux of the push piston 41 reaches a threshold value, it indicates that the injection member 42 has been home to the safe position and sends a status confirmation signal to an external control system (not shown), as shown in Figure 6

[0065] In another embodiment, the injection member 42 of the present application can be made of a degradable material that degrades after piercing the intestinal wall tissue. In this case, the home assembly and the sensing portion can be omitted.

[0066] As shown in Figure 7 the balloon 1 has been pierced by the injection member, the carbon dioxide gas in the balloon will slowly escape, the balloon volume slowly shrinks, until the carbon dioxide gas in the balloon is completely exhausted, the balloon is tightly wrapped on the surface of the capsule due to its own elastic effect, and the entire drug delivery process is completed. The delivery capsule will be discharged from the body together with the feces.

[0067] Those skilled in the art will understand that the foregoing examples are exemplary and not limiting. It will be apparent to those skilled in the art, upon reading the specification and studying the drawings, that all permutations, enhancements, equivalents, and improvements are included within the true spirit and scope of the present application. Accordingly, the appended claims are intended to encompass all such modifications, permutations, equivalents, and improvements as fall within the true spirit and scope of these teachings.

[0068] BRIEF DESCRIPTION OF DRAWINGS

[0069] 1 balloon

[0070] 10 protective shell

[0071] 12 injection hole

[0072] 2 shaped support

[0073] 3 trigger pod

[0074] 31 trigger mechanism

[0075] ​311 actuation mechanism

[0076] 312 carrier

[0077] 312a umbrella barb

[0078] 313 vent

[0079] 32 push piston

[0080] 32a positioning hole

[0081] 4 propulsion compartment

[0082] 41 propulsion piston

[0083] 42 injection component

[0084] 43 homing assembly

[0085] 5 formulation compartment

[0086] 6 sensing portion

[0087] 61 sensing assembly

[0088] 7 intestinal tract

Claims

1. An in vivo drug delivery device, characterized in that, include: An inflatable balloon (1) has a protective shell (10) on at least a portion of its outer wall, the balloon having an inner cavity, and the protective shell (10) being soluble in bodily fluids. The trigger part (3) is provided in the inner cavity of the balloon. The trigger part (3) can react with the body fluid when in contact with the body fluid to generate fluid to inflate the balloon, so that the inflated balloon is in close contact with the body cavity wall. The propulsion section within the inner cavity of the balloon includes a tissue-penetrating member, and the triggering section is capable of generating power to propel the tissue-penetrating member. as well as The container section is used to contain pharmaceutical preparations. The triggering part is capable of pushing the liquid drug preparation contained in the receiving part into the propulsion part after the balloon is inflated, and injecting the liquid drug preparation into the tissue wall of the human cavity through the tissue penetration member.

2. The drug delivery device according to claim 1, characterized in that, The body fluid in question is small intestinal fluid.

3. The drug delivery device according to claim 1, characterized in that, The tissue-penetrating component is an injection component (42).

4. The drug delivery device according to claim 3, characterized in that, The injection component (42) is made of a biodegradable material.

Images