Drug delivery devices in the human body

Abstract

The present invention discloses a drug delivery device in a human cavity, which comprises: an inflatable balloon, at least a portion of the outer wall of the balloon is provided with a protective shell, the balloon has an inner cavity, and the protective shell can be dissolved by a specific body fluid in the human cavity; a triggering part arranged in the inner cavity of the balloon, the triggering part can react with the body fluid to generate a fluid to inflate the balloon when in contact with the body fluid, so that the inflated balloon is close to the body cavity wall; a propulsion part in the inner cavity of the balloon, the propulsion part includes a tissue penetrating member, the triggering part can generate power to propel the tissue penetrating member; and a containing part for containing a drug preparation, wherein the triggering part can push the liquid drug preparation contained in the containing part into the propulsion part after the balloon is inflated, and inject the liquid drug preparation into the inner wall tissue of the human cavity through the tissue penetrating member. The device of the present invention can be used to inject macromolecular drugs or preparations into the inner wall of the human cavity, such as the tissue of the intestinal wall.

Description

Technical Field

[0001] The present invention relates to a drug delivery device, in particular to a drug delivery device capable of injecting macromolecular drugs or preparations into the inner wall tissue of a cavity in a human body. Background Art

[0002] With the development of biotechnology, there are more and more biological preparations based on oligonucleotides, proteins, peptides and other macromolecules. The route of administration is a common problem encountered by biological preparations in clinical applications. Because biological preparations are easily degraded in the liver and gastrointestinal tract when taken orally, reducing the effective bioavailability of biological preparations; it is difficult to maintain a stable blood drug concentration in the body when injected, and frequent injections will also cause great inconvenience and pain to the recipients. At the same time, they also have to face the situation that there is no drug available for those who are intolerant of intravenous injections; transdermal administration is also restricted by the large molecular weight of biological preparations, and it is difficult to penetrate through the stratum corneum of the skin and enter the human circulatory system. Therefore, the small intestinal lining injection of macromolecule preparations in the natural cavity of the body as an innovative drug delivery method other than conventional oral, in vitro injection and transdermal administration will create a new drug delivery method.

[0003] Compared with common drug delivery methods, intracavitary wall injection has the following advantages:

[0004] (1) It solves the problem of no drug available for patients who are intolerant to intravenous administration and avoids various adverse reactions of intravenous infusion.

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

[0006] (3) Provide a gentle drug administration method to improve the recipient experience.

[0007] (4) It avoids the patient's fear of regular injections and effectively improves the patient's compliance. Summary of the invention

[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 the inner wall tissue of a human cavity.

[0009] To this end, the present invention provides a drug delivery device for injecting into the inner wall of a human cavity, comprising: an inflatable balloon, at least a portion of the outer wall of the balloon is provided with a protective shell, the balloon has an inner cavity, and the protective shell can be dissolved by body fluids in the human body; a trigger portion arranged in the inner cavity of the balloon, the trigger portion 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 wall of the body cavity; a propulsion portion in the inner cavity of the balloon, the propulsion portion includes a tissue penetrating member, the trigger portion can generate power to propel the tissue penetrating member; and a containing portion for containing a drug preparation, wherein the trigger portion can push the liquid drug preparation contained in the containing portion into the propulsion portion after the balloon is inflated, and inject the liquid drug preparation into the human tissue through the tissue penetrating member.

[0010] Preferably, the drug delivery device further comprises a restriction element disposed on the outer surface of the balloon, wherein the restriction element is used to control the inflation deformation of the balloon.

[0011] Preferably, the limiting element is a shaping stent, which is fixed on part of the outer surface of the balloon, so that the part of the balloon in the gap of the shaping stent is allowed to expand and deform, and the part of the balloon on which the shaping stent is fixed is abutted against the body wall and the injection position of the drug preparation is in this part.

[0012] Preferably, the trigger portion includes a trigger cabin, a trigger mechanism disposed in the trigger cabin, and a pushing member triggered by the trigger mechanism.

[0013] Preferably, the trigger mechanism comprises a transmitter, and after the protective shell is dissolved, the transmitter contacts body fluids to react and release gas to inflate the balloon.

[0014] Preferably, the pushing member is a pushing piston, which can move along the balloon at a certain angle, preferably longitudinally, but is held fixed by the transmitter before the transmitter reacts, and is released after the transmitter reacts.

[0015] Preferably, the transmission body and the pushing piston are kept in a locked state by shape fit.

[0016] Preferably, the trigger mechanism further comprises an actuating mechanism arranged between the trigger bulkhead and the pushing assembly. In an initial state, the actuating mechanism is in an unactivated state, i.e., a locked state. After the trigger mechanism is started, the actuating mechanism is activated to cause the pushing component to move and generate pressure on the accommodating portion.

[0017] Preferably, the communication body is made of a material that reacts when in contact with water.

[0018] Preferably, the actuating mechanism is a compression spring, or other mechanism capable of generating pressure such as a compression airbag.

[0019] Preferably, the propulsion portion includes a propulsion mechanism, which has a propulsion piston, and the tissue penetrating member is fixedly mounted on the propulsion piston. In an initial state, the tissue penetrating member is accommodated in the propulsion cabin, and in a working state, the propulsion piston and the tissue penetrating member are pushed outward together, and the tissue penetrating member pierces the balloon, allowing the liquid drug preparation to be injected into the inner wall tissue of the human cavity through the tissue penetrating member.

[0020] Preferably, the advancement piston and the tissue penetrating member are pushed out under the pressure of the drug formulation.

[0021] Preferably, the advancement mechanism further comprises a return assembly, which returns the advancement piston to its original position and retracts the tissue penetrating member into the advancement chamber when the injection is completed.

[0022] Preferably, the return assembly is a tension spring fixed between the propulsion piston and the bulkhead of the propulsion portion, or a mechanism capable of generating pressure.

[0023] Preferably, the advancement piston moves in a direction forming a certain angle with the longitudinal direction of the balloon, so that the movement direction of the tissue penetrating member forms a certain angle with the longitudinal direction.

[0024] Preferably, the angle between the moving direction of the tissue penetrating member and the longitudinal direction is 45° to 135°.

[0025] Preferably, the drug delivery device further comprises: a sensing component disposed near the propulsion chamber, for sensing the position of the propulsion piston and / or the tissue penetrating member, so as to confirm that the tissue penetrating member is returned to a safe position.

[0026] Preferably, the sensing component comprises a sensor, and a sensing marker is provided on the advancement piston and / or the tissue penetrating member, and the sensing component is used to detect whether the sensing marker reaches a threshold value to confirm the position of the advancement piston.

[0027] Preferably, the sensing marker comprises a magnetic material, and the sensing component is used to detect magnetic flux.

[0028] Preferably, the body fluid is intestinal fluid.

[0029] Preferably, the tissue penetrating member is an injection component.

[0030] Preferably, the injection component is made of a degradable material.

[0031] The present invention has the following beneficial effects.

[0032] 1. The delivery device of the present invention can be used to achieve direct injection administration in the human body, avoiding adverse reactions such as intravenous injection.

[0033] 2. The delivery device of the present invention can ensure that the drug is reliably injected into the intestinal wall.

[0034] 3. The delivery device of the present invention can ensure that the injection component is retracted after the injection is completed through the return component to avoid causing personal injury.

[0035] 4. The present invention further comprises a sensor part to detect the position of the injection component and confirm whether the injection component is retracted. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 is a schematic diagram of a drug delivery device of the present invention.

[0037] Figure 2 Schematic diagram of a drug delivery device positioned within a lumen (eg, the small intestine).

[0038] Figure 3 Schematic diagram of the drug delivery device after it comes into contact with intestinal fluid, the protective shell breaks down and the balloon begins to inflate.

[0039] Figure 4 Schematic diagram of performing an injection for a drug delivery device.

[0040] Figure 5 Schematic diagram of the drug delivery device in which the injection component starts to retract after the injection is completed.

[0041] Figure 6 Schematic diagram of the injection component of the drug delivery device being fully returned to its original position.

[0042] Figure 7 Schematic diagram of the capsule being deflated and retracted so that the drug delivery device can be expelled from the body.

[0043] To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements disclosed in one embodiment may be beneficially utilized on other embodiments without specific recitation. DETAILED DESCRIPTION

[0044] See also Figure 1 The in vivo drug delivery device of the present invention has a shape similar to a capsule or a pill, and therefore, can also be referred to as a delivery capsule, or simply a capsule.

[0045] like Figure 1As shown, the delivery capsule according to the present invention includes 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 after the delivery capsule enters the human body, it is not affected in the stomach, and enters the human intestine 7, such as the small intestine, and starts to work 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 tract or body cavity locations, and the present invention is not limited thereto.

[0046] The balloon 1 is made of a material that can be stretched during and / or after inflation. A structure for controlling the deformation and expansion of the balloon is provided on the balloon 1. The structure for controlling the deformation and expansion of the balloon can be a rigid limiting element. In the present embodiment, the limiting element is a shaping bracket 2, which is clamped on a portion of the outer surface of the balloon 1. This portion of the outer surface is constrained by the shaping bracket 2 and cannot be deformed freely. The remaining portion of the balloon 1 that is not constrained by the shaping bracket 2 can be freely expanded and deformed in the gap of the shaping bracket 2 due to the air pressure inside the balloon. When the balloon is inflated, the portion of the balloon on which the shaping bracket 2 is fixed can be pressed against the body wall, and the injection position (especially the injection hole) of the drug preparation is located in this portion. From Figure 1 As can be seen in the figure, the shaping bracket 2 is arranged on the upper part of the balloon 1. When the balloon 1 is inflated, its lower part can abut against the intestinal wall and push the part where the shaping bracket 2 is arranged to abut against the intestinal wall, so that the position where the drug preparation is to be injected, that is, the injection hole 12, can reliably contact the intestinal wall (see Figure 3 ).

[0047] The balloon 1 has an inner cavity, in which a triggering part, a propulsion part and a receiving part are arranged. The triggering part can react with body fluid when in contact with it, generate fluid to inflate the balloon, so that the inflated balloon is close to the wall of the body cavity. The propulsion part includes a tissue penetrating member, and the triggering part can generate power to propel the tissue penetrating member. The receiving part is used to contain a fluid drug preparation.

[0048] After the balloon is inflated, the trigger portion pushes the fluid drug preparation contained in the containing portion into the propulsion chamber 4, and injects the liquid drug preparation into the human body through the tissue penetrating member.

[0049] In this embodiment, the triggering part is a triggering cabin 3 arranged on the first side (the left side in the figure) along the longitudinal direction (or axial direction) of the inner cavity; the propulsion part includes a propulsion cabin 4 arranged on the second side (the right side in the figure); the accommodating part is arranged between the triggering cabin 3 and the propulsion cabin 4, which can also be called a preparation cabin 5. A sensing part 6 is arranged around the propulsion cabin 4 (for example, the inside or outside, the outside in this embodiment).

[0050] The trigger chamber 3 includes a trigger mechanism 31 and a pushing member. In this embodiment, the pushing member is a pushing piston 32. The trigger 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 chamber 5 into the propulsion chamber 4, and enables the propulsion mechanism in the propulsion chamber 4 to inject the drug preparation into the human body.

[0051] In this embodiment, the trigger mechanism 31 includes a transmission body 312 and an actuating mechanism 311 .

[0052] The transmission body 312 is made of a material that reacts with water and is covered in the protective shell 10. When the protective shell 10 dissolves, the transmission 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.

[0053] like Figure 3 As shown, due to the restriction of the shaping support 2, the balloon 1 will expand toward the gap of the shaping support 2 (the lower part in the figure), and this expansion posture will push the delivery capsule to one side of the intestine and make the injection hole 12 of the delivery capsule close to the intestinal wall, so as to prepare for the tissue penetrating member (injection component) to reliably penetrate the intestinal wall. The injection hole 12 is closed before being punctured by the injection component.

[0054] As the reaction of the transmission body 312 proceeds, the actuating mechanism 311 is activated to provide pressure to the pushing piston 32. More specifically, the actuating mechanism 311 is disposed between the triggering compartment wall and the pushing piston 32 and is in an inactive state, i.e., a locked state. In the initial state, the pushing piston 32 is constrained by the transmission body 312. When the transmission body 312 reacts and dissolves, the pushing piston 32 loses its constraint, and the actuating mechanism 311 pushes toward the preparation compartment 5 in the longitudinal direction.

[0055] In this embodiment, the actuating mechanism 311 is a compression spring. In the initial state, the compression spring is biased in a compressed state to accumulate bias force. After the trigger mechanism 31 is triggered and the transmission body 312 is dissolved, the compression spring releases the bias force, so that the pushing piston 32 moves along the balloon at a certain angle, preferably moves in the longitudinal direction, and pushes the preparation chamber 5. The actuating mechanism 311 can also be other elements, such as a material that rapidly expands when exposed to water or a highly explosive material that can push the pushing piston 32 to move quickly in the longitudinal direction, or other mechanisms that can generate pressure such as a compression airbag, and the present invention is not limited thereto.

[0056] The transmission body 312 and the pushing piston 32 are matched in shape to hold the pushing piston 32. As the transmission body 312 dissolves, the transmission body 312 can no longer constrain the pushing piston 32 and release it. In this embodiment, the front end of the transmission body 312 forms an umbrella-shaped barb 312a, which is embedded in the positioning hole 32a of the pushing piston 32. As the transmission body 312 dissolves, the umbrella-shaped barb 312a gradually disengages from the positioning hole 32a, thereby releasing the pushing piston 32. The transmission body 312 and the pushing piston can also be locked together in other ways, and the pushing piston 32 is released after the transmission body 312 dissolves, and the present invention is not limited thereto.

[0057] The preparation chamber 5 is used to contain a liquid preparation. When the pushing piston 32 is pushed forward, the liquid preparation transmits pressure to the pushing chamber 4 .

[0058] The propulsion chamber 4 includes a propulsion mechanism and a homing assembly 43. In this embodiment, the propulsion mechanism includes a propulsion piston 41 and a tissue penetrating member, such as an injection component 42. The injection component 42 is mounted on the propulsion piston 41 and moves with the propulsion piston 41 in a direction that is at a certain angle to the longitudinal direction, such as in a range of 45° to 135°, preferably 90°. In an initial state when not activated, the injection component 42 is closed and stored inside the propulsion chamber.

[0059] like Figure 4 As shown, when the preparation chamber 5 is pressurized, the liquid drug preparation will transfer the pressure to the propulsion chamber 4, and the propulsion piston 41 will move outward under the pressure, so that the injection component 42 will pierce the balloon 1 outward from the injection hole of the delivery capsule. Since the injection hole 12 of the delivery capsule is already close to the intestinal wall at this time, the injection component 42 will pierce the intestinal wall and inject the preparation into the intestinal wall tissue. In this embodiment, the return component 43 is a tension spring fixed between the propulsion piston and the wall of the propulsion chamber, and when the propulsion piston 41 moves outward, the tension spring is compressed.

[0060] like Figure 5 As shown, after the injection is completed, the pressure in the preparation chamber 5 decreases due to the emptying of the preparation, 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 in the preparation chamber 5 is balanced with the external pressure, the return assembly 43 will return the injection component 42 to a safe position in the delivery capsule propulsion chamber.

[0061] The return component 43 may also be other than a tension spring, for example, magnetic components are respectively provided on the propulsion piston 41 and the propulsion cabin wall, so that a repulsive force is formed between the two, and when the injection is completed, the repulsive force can return the injection component 42 to its original position. Alternatively, the tension spring may be replaced by other restoring components with restoring force, which is not limited by the present invention.

[0062] In order to confirm whether the injection component 42 is completely returned to its original position, a sensing part 6 is provided near the propulsion cabin 4. In the present embodiment, the sensing part 6 is formed on the outside of the propulsion cabin 4, i.e., the end of the capsule. However, the sensing part 6 may also be formed on the inside of the propulsion cabin 4 or at other positions, and the present invention is not limited thereto. A sensing component 61 is installed in the sensing part 6 for sensing the return state of the pushing piston 32 in the propulsion cabin and the injection component 42 in the propulsion cabin 4. In the present embodiment, the sensing component 61 is a sensor, in which a sensor chip is provided for sensing the position of the propulsion piston 41. A sensing marker is provided on the propulsion piston 41.

[0063] In this embodiment, the propulsion piston 41 is made of magnetic material or contains magnetic material. When the sensing component 61 senses that the magnetic flux of the propulsion piston 41 reaches a threshold value, it indicates that the injection component 42 has returned to a safe position and sends a status confirmation signal to an external control system (not shown). Figure 6 shown.

[0064] In another embodiment, the injection component 42 of the present invention can be made of a degradable material and degraded after piercing the intestinal wall tissue. In this case, the homing component and the sensor part can be omitted.

[0065] like Figure 7 As shown, since balloon 1 has been punctured by the injection component, the carbon dioxide gas in the balloon will be slowly discharged, and the volume of the balloon will slowly shrink until the carbon dioxide gas in the balloon is completely discharged and the balloon is tightly wrapped on the capsule surface due to its own elasticity. At this point, the entire drug delivery process is completed, and the delivery capsule will be discharged from the body through the colon together with feces.

[0066] Those skilled in the art will appreciate that the foregoing examples are illustrative and not restrictive. 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 invention. Therefore, the appended claims are intended to include all such modifications, permutations, and equivalents that fall within the true spirit and scope of these teachings.

[0067] Description of Reference Numerals

[0068] 1 Balloon

[0069] 10. Protective case

[0070] 12 Injection hole

[0071] 2. Forming bracket

[0072] 3 Trigger Pod

[0073] 31 Trigger mechanism

[0074] 311 Actuating mechanism

[0075] 312 Communication

[0076] 312a Umbrella Barb

[0077] 313 Exhaust Hole

[0078] 32 Push piston

[0079] 32a Positioning hole

[0080] 4 Propulsion module

[0081] 41 Thrust piston

[0082] 42 Injection parts

[0083] 43 Home component

[0084] 5 Preparation Chamber

[0085] 6. Sensor

[0086] 61 Sensor components

[0087] 7. Intestines

Claims

1. An in vivo drug delivery device, comprising: An inflatable balloon (1) having an inner cavity, a propulsion portion in the lumen of the balloon, the propulsion portion comprising a tissue penetrating member, Features: At least a portion of the outer wall of the balloon is provided with a protective shell (10), and the protective shell (10) can be dissolved by body fluids in the human body; A triggering portion (3) is arranged in the inner cavity of the balloon, and the triggering portion (3) can react with body fluid to generate gas to inflate the balloon when in contact with the body fluid, so that the inflated balloon is closely attached to the wall of the body cavity; The trigger portion is capable of generating power to advance the tissue penetrating member; and a containing portion for containing a drug preparation, The triggering part can push the liquid drug preparation contained in the containing part into the propulsion part after the balloon is inflated, and inject the liquid drug preparation into the inner wall tissue of the human cavity through the tissue penetrating member. The propulsion unit comprises a propulsion mechanism and a propulsion chamber (4), the propulsion mechanism having a propulsion piston (41), the tissue penetrating member being fixedly mounted on the propulsion piston; 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 outward together, the tissue penetrating member punctures the balloon, and allows a liquid drug preparation to be injected into the inner wall tissue of a human cavity through the tissue penetrating member.

2. The drug delivery device according to claim 1, characterized in that It also includes a limiting element arranged on the outer surface of the balloon, and the limiting element is used to control the inflation deformation of the balloon.

3. The drug delivery device according to claim 2, characterized in that The limiting element is a shaping bracket (2), which is fixed on part of the outer surface of the balloon, so that the part of the balloon in the gap of the shaping bracket is allowed to expand and deform, and the part of the balloon on which the shaping bracket is fixed is abutted against the body wall and the injection position of the drug preparation is located in this part.

4. The drug delivery device according to claim 1, 2 or 3, characterized in that: The trigger portion comprises a trigger chamber, a trigger mechanism (31) arranged in the trigger chamber, and a pushing component triggered by the trigger mechanism.

5. The drug delivery device according to claim 4, characterized in that The trigger mechanism (31) comprises a transmitter (312). After the protective shell is dissolved, the transmitter (312) contacts body fluids to react and release gas to inflate the balloon (1).

6. The drug delivery device according to claim 5, characterized in that The pushing member is a pushing piston (32), and the pushing piston (32) can move along the balloon at a certain angle, but before the transmission body (312) reacts, the pushing piston is held fixed by the transmission body (312), and after the transmission body (312) reacts, the pushing piston is released.

7. The drug delivery device according to claim 6, characterized in that The pushing piston (32) can move along the longitudinal direction of the balloon.

8. The drug delivery device according to claim 6, characterized in that The transmission body (312) and the pushing piston (32) are kept in a locked state through shape matching.

9. The drug delivery device according to claim 4, characterized in that The trigger mechanism also includes an actuating mechanism (311) arranged between the trigger bulkhead and the pushing assembly. In an initial state, the actuating mechanism is in an unactivated state, i.e., a locked state. After the trigger mechanism is started, the actuating mechanism is activated to cause the pushing component to move and generate pressure on the accommodating portion.

10. The drug delivery device according to claim 5, characterized in that The transmission body is made of a material that reacts when in contact with water.

11. The drug delivery device according to claim 9, characterized in that The actuating mechanism is a compression spring or a compression air bag.

12. The drug delivery device according to claim 1, characterized in that The advancing piston (41) and the tissue penetrating member are pushed out under the pressure of the drug preparation.

13. The drug delivery device according to claim 1, characterized in that The propulsion mechanism further comprises a return assembly (43), which returns the propulsion piston to its original position and retracts the tissue penetrating member into the propulsion chamber when the injection is completed.

14. The drug delivery device according to claim 13, characterized in that The return assembly is a tension spring fixed between the propulsion piston (41) and the bulkhead of the propulsion part.

15. The drug delivery device according to claim 1, characterized in that The advancement piston moves in a direction that is at a certain angle to the longitudinal direction of the balloon, so that the movement direction of the tissue penetrating member is at a certain angle to the longitudinal direction.

16. The drug delivery device according to claim 15, characterized in that The angle between the moving direction of the tissue penetrating member and the longitudinal direction is 45° to 135°.

17. The drug delivery device according to claim 1, characterized in that Also includes: A sensing component disposed near the propulsion chamber is used to sense the position of the propulsion piston and / or the tissue penetrating member to confirm that the tissue penetrating member has returned to a safe position.

18. The drug delivery device according to claim 17, characterized in that The sensing component includes a sensor, and a sensing marker is provided on the advancement piston and / or the tissue penetrating member. The sensing component is used to detect whether the sensing marker reaches a threshold value to confirm the position of the advancement piston.

19. The drug delivery device according to claim 18, characterized in that The sensing marker includes a magnetic material, and the sensing component is used to detect magnetic flux.

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

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

22. The drug delivery device according to claim 21, characterized in that The injection component (42) is made of a degradable material.

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