In vivo drug delivery device

Abstract

An in vivo drug delivery device, comprising: an inflatable balloon (1), wherein at least a part of the outer wall of the balloon (1) is provided with a protective shell (10), the balloon (1) has an inner cavity, and the protective shell (10) can be dissolved by body fluids in the human body; a trigger portion, which is provided in the inner cavity of the balloon, wherein the trigger portion can react with the body fluids when in contact, so as to generate a fluid to inflate the balloon (1), such that the inflated balloon (1) abuts against the wall of the cavity; a pushing portion in the inner cavity of the balloon (1), wherein the pushing portion comprises a tissue penetrating member and a trigger portion capable of generating power to push the tissue penetrating member; and an accommodating portion for accommodating a drug formulation. After the balloon (1) is inflated, the trigger portion can push the liquid drug formulation accommodated in the accommodating portion into the pushing portion, and by means of the tissue penetrating member the liquid drug formulation is injected into human tissues. The in vivo drug delivery device is capable of injecting a macromolecular drug or formulation into tissues of the intestinal wall.

Description

Drug delivery device in human body TECHNICAL FIELD

[0001] The present invention relates to a drug delivery device, in particular, a drug delivery device capable of injecting a macromolecular drug or preparation into tissue in human body. BACKGROUND

[0002] With the development of biotechnology, more and more biological preparations mainly in the form of oligonucleotides, proteins, polypeptides, etc. are used in clinical applications. The drug delivery route is a common problem encountered in the clinical application of biological preparations. Because the biological preparations are easily degraded in the liver and gastrointestinal tract when taken orally, the effective bioavailability of the biological preparations is reduced. When injected, it is difficult to maintain a stable blood drug concentration in the body, and frequent injection will cause great inconvenience and pain to the recipients. At the same time, the patients who are not tolerant to intravenous injection have no drug to use. Transdermal drug delivery is also restricted by the large molecular weight of the 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 of 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.

[0003] Compared with the conventional drug delivery method, the small intestinal wall injection drug delivery has the following advantages:

[0004] (1) Solving the problem of no drug available for patients who are not tolerant to intravenous injection, avoiding various adverse reactions of intravenous infusion.

[0005] (2) Avoiding the liver "first pass effect" and gastrointestinal inactivation that may occur when the drug is taken orally, improving the bioavailability and therapeutic effect.

[0006] (3) Providing a mild drug delivery method to improve the experience of the recipients.

[0007] (4) Avoiding the fear of frequent injection of the recipients, effectively improving the compliance of the recipients. SUMMARY

[0008] The technical problem to be solved by the present invention is to provide a drug delivery device capable of directly injecting a drug into tissue in human body.

[0009] To this end, the present application provides an in-vivo drug delivery device, 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 a body fluid in a human body; a trigger portion provided in the inner cavity of the balloon, the trigger portion being capable of generating a fluid to inflate the balloon when contacted by the body fluid, so that the inflated balloon is tightly attached to the wall of a 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.

[0010] Further comprising a limiting element provided on the outer surface of the balloon, the limiting element being used to control the inflation deformation of the balloon.

[0011] 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 the portion.

[0012] 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.

[0013] Preferably, the trigger mechanism comprises a transmission body, the transmission body being capable of contacting the body fluid and swelling after the protective shell is dissolved.

[0014] Preferably, the pushing member is a pushing piston, the pushing piston being capable of moving along the longitudinal direction of the balloon.

[0015] Preferably, the trigger mechanism further comprises an actuating mechanism provided between the wall of the trigger cabin and the pushing assembly, the actuating mechanism being in an inactivated state in an initial state, and the actuating mechanism being activated to cause the pushing member to move to generate pressure on the containing portion after the trigger mechanism is started.

[0016] Preferably, the transmission body is made of a water-soluble material.

[0017] Preferably, the actuating mechanism is a compression spring.

[0018] Preferably, the propelling part comprises a propelling mechanism, the propelling mechanism further comprises a propelling piston, the tissue-penetrating member is fixedly installed on the propelling piston, in the initial state, the tissue-penetrating member is accommodated in the propelling cabin, in the working state, the propelling piston and the tissue-penetrating member are pushed out together, the tissue-penetrating member pierces the balloon, and the liquid drug preparation can be injected into the human tissue through the tissue-penetrating member.

[0019] Preferably, the propelling piston and the tissue-penetrating member are pushed out under the pressure of the drug preparation.

[0020] Preferably, the propelling mechanism further comprises a homing assembly, when the injection is completed, the homing assembly makes the propelling piston return to the original position and makes the tissue-penetrating member retract into the propelling cabin.

[0021] Preferably, the homing assembly is a tension spring fixed between the propelling piston and the cabin wall of the propelling part.

[0022] Preferably, the propelling piston moves transversely to the longitudinal movement of the balloon, so that the moving direction of the tissue-penetrating member is at an angle to the longitudinal direction.

[0023] Preferably, the angle between the moving direction of the tissue-penetrating member and the longitudinal direction is 45° to 135°.

[0024] Preferably, the drug delivery device further comprises a sensing assembly arranged near the propelling cabin, for sensing the position of the propelling piston and / or the tissue-penetrating member, to confirm that the tissue-penetrating member returns to the safe position.

[0025] Preferably, the sensing assembly comprises a sensor, and a sensing marker is arranged on the propelling piston and / or the tissue-penetrating member, and the sensing assembly is used to detect whether the sensing marker reaches a threshold value to confirm the position of the propelling piston.

[0026] Preferably, the sensing marker comprises a magnetic material, and the sensing assembly is used to detect the magnetic flux.

[0027] Preferably, the body fluid is small intestinal fluid.

[0028] Preferably, the tissue-penetrating member is an injection part.

[0029] Preferably, the injection part is made of degradable material.

[0030] The present application has the following beneficial effects.

[0031] 1. The delivery device of the present application can realize direct injection in the human body, avoiding the adverse reactions of intravenous injection, etc.

[0032] 2. By the delivery device of the present application, it is ensured that the drug is reliably injected into the intestinal wall.

[0033] 3. By the homing assembly of the delivery device of the present application, it is ensured that the injection member is retracted after the injection is completed, so as to avoid causing personal injury.

[0034] 4. The present application further comprises a sensing portion to detect the position of the injection member, so as to confirm whether the injection member is retracted. BRIEF DESCRIPTION OF DRAWINGS

[0035] Fig. 1 is a schematic view of the drug delivery device of the present application.

[0036] Fig. 2 is a schematic view of the drug delivery device located in a body cavity, such as the small intestine.

[0037] Fig. 3 is a schematic view of the drug delivery device after the protective shell is disintegrated and the balloon starts to inflate after contacting the small intestinal fluid.

[0038] Fig. 4 is a schematic view of the drug delivery device performing injection.

[0039] Fig. 5 is a schematic view of the drug delivery device after the injection is completed, and the injection member starts to retract.

[0040] Fig. 6 is a schematic view of the drug delivery device after the injection member is completely homed.

[0041] Fig. 7 is a schematic view of the capsule deflation and retraction, so as to expel the drug delivery device out of the body.

[0042] For the sake of convenience, the same reference numerals are used in the drawings and the description to indicate the same elements among the figures. It is contemplated that elements disclosed in one embodiment can be advantageously used in other embodiments without specific recitation. DETAILED DESCRIPTION

[0043] Referring to Fig. 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.

[0044] As shown in Fig. 1, the delivery capsule according to the present application comprises a balloon 1, and at least a portion of the outer wall of the balloon 1 is provided with a protective shell 10. In this 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 only starts to act after contacting the small intestinal fluid in the intestinal tract 7, such as the small intestine, of the human body. 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 is not limited thereto.

[0045] 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 this embodiment, the limiting element is a shaping stent 2, which is clamped on a part of the outer surface of the balloon 1, which part is constrained by the shaping stent 2 and cannot freely deform. The rest of the balloon 1, which 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 in the balloon. When the balloon expands, the part of the balloon on which the shaping stent 2 is fixed can be attached to the body wall and the injection site of the drug preparation (especially the injection hole) is in this part. As can be seen from Figure 1, 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 be attached to the intestinal wall and push the part provided with the shaping stent 2 to attach to the intestinal wall, so that the injection site of the drug preparation, i.e. the injection hole 12, can reliably contact the intestinal wall (see Figure 3).

[0046] The balloon 1 has an inner cavity, in which a triggering part, a propelling part and a containing part are arranged. The triggering part can react with the body fluid when it contacts the body fluid to generate a fluid to inflate the balloon, so that the inflated balloon is attached to the body cavity wall. The propelling part includes a tissue penetrating member, and the triggering part can generate power to propel the tissue penetrating member. The containing part is used to contain the fluid drug preparation.

[0047] The triggering part pushes the fluid drug preparation contained in the containing part into the propelling cabin 4 after the balloon is inflated, and injects the liquid drug preparation into the human body through the tissue penetrating member.

[0048] In this embodiment, the triggering part is a triggering cabin 3 arranged on the first side (left side in the figure) of the inner cavity in the longitudinal direction (or axial direction); the propelling part includes a propelling cabin 4 arranged on the second side (right side in the figure); the containing part is arranged between the triggering cabin 3 and the propelling cabin 4, which can also be referred to as a preparation cabin 5. The sensing part 6 is arranged around (for example, on the inner side or the outer side, in this embodiment, on the outer side) the propelling cabin 4.

[0049] The triggering cabin 3 includes a triggering mechanism 31 and a pushing member. In this embodiment, the pushing member is a pushing piston 32. The triggering mechanism 31 can be triggered after the protective shell 10 is dissolved and contacts the body fluid, and pushes the drug preparation contained in the preparation cabin 5 into the propelling cabin 4, and makes the propelling mechanism in the propelling cabin 4 inject the drug preparation into the human body.

[0050] In this embodiment, the triggering mechanism 31 includes a transmission body 312 and an actuating mechanism 311.

[0051] The delivery body 312 is made of water-soluble fiber and is covered in the protective shell 10. When the protective shell 10 dissolves, the delivery body 312 releases a large amount of gas (e.g., carbon dioxide) and water upon contact with moisture in the body fluid. The gas enters the balloon 1 from the gas vent 313, causing the balloon 1 to expand.

[0052] As shown in Fig. 3, due to the restriction of the shaping support 2, the balloon 1 will expand toward the gap portion of the shaping support 2 (lower portion in the figure), and this expanded position will push the delivery capsule toward one side of the intestinal tract and press the injection hole 12 portion of the delivery capsule against the intestinal wall, thus preparing the tissue-penetrating member (injection member) for reliable penetration into the intestinal wall. The injection hole 12 is closed until it is punctured by the injection member.

[0053] 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 disposed between the trigger compartment wall and the push piston 32 in an inactivated state. The push piston 32 is initially constrained by the delivery body 312, and when the delivery body 312 dissolves due to the reaction, the push piston 32 is released from the constraint, and the actuating mechanism 311 pushes the push piston 32 in the longitudinal direction toward the formulation compartment 5.

[0054] In the present embodiment, the actuating mechanism 311 is a compression spring that is biased in a compressed state to accumulate biasing force in the initial state. When the trigger mechanism 31 is triggered and the delivery body 312 dissolves, the compression spring releases the biasing force, causing the push piston 32 to push the formulation compartment 5 in the longitudinal direction. The actuating mechanism 311 can also be other elements, such as a water-reactive material that swells sharply or a high-explosive material that can push the push piston 32 to move rapidly in the longitudinal direction, and the present application is not limited in this respect.

[0055] The delivery body 312 and the push piston 32 are held together by a shape fit. As the delivery body 312 dissolves, the delivery body 312 is no longer able to constrain the push piston 32 and releases it. In the present embodiment, the front end of the delivery body 312 is formed as an umbrella-shaped barb 312a that is embedded in a positioning hole 32a of the push piston 32. As the delivery body 312 dissolves, the umbrella-shaped barb 312a gradually comes off the positioning hole 32a, thereby releasing the push piston 32. The delivery body 312 and the push piston 32 can be held together in other ways and released from each other upon dissolution of the delivery body 312, and the present application is not limited in this respect.

[0056] The formulation compartment 5 is used to contain a liquid formulation, and when the push piston 32 is pushed, the liquid formulation transmits pressure to the propulsion compartment 4.

[0057] The propulsion compartment 4 comprises a propulsion mechanism and a homing assembly 43. In the present embodiment, the propulsion mechanism comprises a propulsion piston 41 and a tissue-penetrating member, for example an injection member 42. The injection member 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 in the range of 45° to 135°, preferably 90°. In the initial state when the device is not activated, the injection member 42 is enclosed inside the propulsion compartment.

[0058] As shown in Fig. 4, when the formulation compartment 5 is pressurized, the liquid drug formulation will transfer the pressure to the propulsion compartment 4, and the propulsion piston 41 will move outward under the pressure, causing the injection member 42 to pierce the balloon 1 outward from the injection hole site of the delivery capsule. Since the injection hole 12 of the delivery capsule is already in close contact with the intestinal wall at this time, the injection member 42 will pierce into the intestinal wall and inject the formulation into the intestinal wall tissue. In the present embodiment, the homing assembly 43 is a tension spring fixed between the propulsion piston and the propulsion compartment wall, which is compressed when the propulsion piston 41 moves outward.

[0059] As shown in Fig. 5, after the injection is completed, the pressure in the formulation compartment 5 decreases due to the emptying of the formulation, and the outward force of the propulsion piston 41 is also reduced. The homing assembly 43 (i.e. the compressed tension spring) in the propulsion compartment 4 will cause the injection member 42 to withdraw from the intestinal wall tissue and begin to home and retract into the propulsion compartment 1. When the pressure in the formulation compartment 5 is balanced with the external pressure, the homing assembly 43 will cause the injection member 42 to home to a safe position inside the delivery capsule propulsion compartment.

[0060] The homing assembly 43 can also be implemented in other ways other than a tension spring, for example, magnetic components are provided on the propulsion piston 41 and the propulsion compartment wall respectively, so that a repulsive force is formed between them, which can cause the injection member 42 to home after the injection is completed. Alternatively, the tension spring can be replaced by other return components with a restoring force, which is not limited in the present application.

[0061] In order to confirm whether the injection member 42 is completely homed, a sensing portion 6 is provided near the propulsion compartment 4. In the present embodiment, the sensing portion 6 is formed on the outside of the propulsion compartment 4, i.e. the end portion of the capsule. However, the sensing portion 6 can also be formed on the inside of the propulsion compartment 4 or other positions, which is not limited in the present application. The sensing portion 6 is provided with a sensing assembly 61 for sensing the homing state of the propulsion piston 32 in the propulsion compartment and the injection member 42 in the propulsion compartment 4. In the present embodiment, the sensing assembly 61 is a sensor provided with a sensing chip for sensing the position of the propulsion piston 41. The propulsion piston 41 is provided with a sensing marker.

[0062] In the present embodiment, the advancing piston 41 is made of or contains magnetic material, and when the sensing assembly 61 senses that the magnetic flux of the advancing piston 41 reaches a threshold value, it indicates that the injection member 42 has been returned to the safe position, and sends a status confirmation signal to the external control system (not shown), as shown in Fig. 6.

[0063] In another embodiment, the injection member 42 of the present application can be made of degradable material, which degrades after penetrating the intestinal wall tissue. In this case, the returning assembly and the sensing part can be omitted.

[0064] As shown in Fig. 7, since the balloon 1 has been punctured by the injection member, the carbon dioxide gas in the balloon will slowly be discharged, and the balloon volume will slowly shrink until the carbon dioxide gas in the balloon is completely discharged, and the balloon is tightly wrapped around the capsule surface due to its own elasticity, thus the entire drug delivery process is completed, and the delivery capsule will be discharged from the body together with the feces.

[0065] Those skilled in the art will understand that the foregoing examples are exemplary and non-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.

[0066] BRIEF DESCRIPTION OF REFERENCE NUMERALS 1 balloon 10 protective shell 12 injection hole 2 shaping support 3 trigger compartment 31 trigger mechanism 311 actuating mechanism 312 transmission body 312a umbrella-shaped barb 313 exhaust hole 32 push piston 32a positioning hole 4 advancing compartment 41 advancing piston 42 injection member 43 returning assembly 5 formulation compartment 6 sensing part 61 sensing assembly 7 intestinal tract

Claims

1. An in vivo drug delivery device, characterized by, The invention relates to a medical device for injecting a liquid drug preparation into a human body tissue, comprising: an inflatable balloon (1) having an outer wall at least partially provided with a protective shell (10) which can be dissolved by a body fluid in the human body, the balloon having an inner cavity, a trigger unit (3) arranged in the inner cavity of the balloon, the trigger unit (3) being capable of generating a fluid to inflate the balloon upon contact with a body fluid, such that the inflated balloon adheres to a body cavity wall, a propulsion unit in the inner cavity of the balloon, the propulsion unit comprising a tissue-penetrating member, the trigger unit being capable of generating a power to propel the tissue-penetrating member, and a holding unit for holding a drug preparation, wherein the trigger unit is capable of pushing the liquid drug preparation held in the holding unit into the propulsion unit after the balloon has been inflated, and injecting the liquid drug preparation into the human body tissue through the tissue-penetrating member.

2. The drug delivery device of claim 1, wherein, Further comprising a limiting element arranged on the outer surface of the balloon, the limiting element being used to control the deformation of the balloon upon inflation.

3. The drug delivery device of claim 2, wherein, The limiting element is a shaped stent (2) fixed on a part of the outer surface of the balloon, such that the part of the balloon in the gap between the shaped stents is allowed to deform upon inflation, while the part of the balloon on which the shaped stents are fixed adheres to the body wall and the injection site of the drug preparation is in this part.

4. The drug delivery device of claim 1, 2 or 3, characterized in that, The trigger unit comprises a trigger chamber and a trigger mechanism (31) arranged in the trigger chamber, and a pushing member triggered by the trigger mechanism.

5. The drug delivery device of claim 4, wherein, The trigger mechanism (31) comprises a messenger (312) which, after the protective shell has been dissolved, contacts the body fluid to react and release gas to inflate the balloon (1).

6. The drug delivery device of claim 5, wherein, The pushing member is a pushing piston (32) which is movable along the longitudinal direction of the balloon, but is held fixed by the messenger (312) before the messenger (312) reacts, and is released after the messenger (312) reacts.

7. The drug delivery device of claim 6, wherein, The messenger (312) and the pushing piston (32) are held fixed by a form fit.

8. The drug delivery device of claim 4, wherein, The trigger mechanism further comprises an actuating mechanism (312) arranged between the wall of the trigger chamber and the pushing assembly, in an initial state, the actuating mechanism is in an inactive state, after the trigger mechanism is activated, the actuating mechanism is activated to cause the pushing member to move to generate pressure on the holding unit.

9. The drug delivery device of claim 5, wherein, The messenger is made of a water-soluble material.

10. The drug delivery device of claim 8, wherein, The actuating mechanism is a compression spring.

11. The drug delivery device of claim 1, wherein, The propulsion unit comprises a propulsion mechanism having a propulsion piston (41) on which the tissue-penetrating member is fixedly mounted, in an initial state, the tissue-penetrating member is accommodated in the propulsion chamber (4), in a working state, the propulsion piston and the tissue-penetrating member are pushed out together, the tissue-penetrating member pierces the balloon, and the liquid drug preparation can be injected into the human body tissue through the tissue-penetrating member.

12. The drug delivery device of claim 10, wherein, The propulsion piston (41) and the tissue-penetrating member are pushed out under the pressure of the drug preparation.

13. The drug delivery device of claim 10, wherein, The propulsion mechanism further comprises a homing assembly (43) which, after the injection is completed, causes the propulsion piston to return to the original position and the tissue-penetrating member to retract into the propulsion chamber.

14. The drug delivery device of claim 13, wherein, The homing assembly is a tension spring fixed between the advancing piston (41) and the hull of the advancing part.

15. The drug delivery device of claim 11, wherein, The advancing piston moves transversely to the longitudinal direction of the balloon, so that the moving direction of the tissue-penetrating member is at an angle to the longitudinal direction.

16. The drug delivery device of claim 14, wherein, The angle between the moving direction of the tissue-penetrating member and the longitudinal direction is 45° to 135°.

17. The drug delivery device of claim 11, wherein, Further comprising: A sensing assembly arranged near the advancing cabin for sensing the position of the advancing piston and / or the tissue-penetrating member to confirm that the tissue-penetrating member is homed to a safe position.

18. The drug delivery device of claim 17, wherein, The sensing assembly comprises a sensor, and a sensing marker is arranged on the advancing piston and / or the tissue-penetrating member, and the sensing assembly is used to detect whether the sensing marker reaches a threshold value to confirm the position of the advancing piston.

19. The drug delivery device of claim 18, wherein, The sensing marker comprises a magnetic material, and the sensing assembly is used to detect the magnetic flux.

20. The drug delivery device of claim 1, wherein, The body fluid is small intestinal fluid.

21. The drug delivery device of claim 1, wherein, The tissue-penetrating member is an injection part (42).

22. The drug delivery device of claim 21, wherein, The injection part (42) is made of a degradable material.

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