An extracranially implemented convection-enhanced delivery device, method, and applications

Abstract

The invention discloses an extracranially implemented convection-enhanced delivery device, comprising an intracranial module and an extracranial module. The extracranial module is connected to the intracranial module, with a fluid delivery channel formed between them. The intracranial module includes a microprobe that can be inserted into target tissue, the distal end of which is equipped with an anatomically compatible sharp penetrating tip. The extracranial module comprises a control pump and a fluid supply tube connected thereto. The fluid supply tube is hermetically connected to the proximal end of the microprobe for delivering drug-containing fluid to the microprobe. An anti-reflux component is provided between the fluid supply tube and the control pump. Compared with existing technologies, the advantages of this invention lie in providing a split-type extracranial-intracranial module design that reduces the volume of implanted objects, lowers infection risks, and facilitates widespread application.

Description

An extracranial convection-enhanced delivery device, method and application TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to an extracranial convection-enhanced delivery device, method and application. BACKGROUND

[0002] Limitations of traditional CED technology: existing CED devices require the pump body and probe to be integrated and implanted intracranially, resulting in large surgical trauma and high risk of infection;

[0003] A single rigid probe cannot adapt to complex brain anatomical structures and is prone to tissue damage, and drug diffusion relies on passive penetration, which is insufficient for deep lesions;

[0004] Meanwhile, the existing device cannot achieve detachable connection between the extracranial module and the intracranial module, resulting in the need for a second surgery to remove the pump body after the operation, and for intracranial use, the probe relies on mechanical propulsion, with a positioning error of >1 mm. SUMMARY

[0005] The technical problem to be solved by the present application is to overcome the above technical defects and provide an extracranial convection-enhanced delivery device, method and application with a split-type extracranial-intracranial module design and easy to popularize and apply.

[0006] To solve the above technical problems, the technical solution provided by the present application is: an extracranial convection-enhanced delivery device, comprising an intracranial module and an extracranial module.

[0007] The extracranial module is connected to the intracranial module, and a liquid supply channel is formed between the extracranial module and the intracranial module.

[0008] Preferably, the intracranial module comprises a microprobe that can be inserted into target tissue, and the distal end of the microprobe further has an anatomically compatible sharp penetrating end.

[0009] Preferably, the extracranial module comprises a control pump and a liquid supply tube connected thereto, the liquid supply tube is sealingly connected to the proximal end of the microprobe, and is used to deliver a drug-containing fluid to the microprobe, and a backflow prevention component is further provided between the liquid supply tube and the control pump.

[0010] Preferably, the sharp penetrating end structure is any one of a conical spiral structure or a magnetic guide tip.

[0011] When the sharp penetrating end structure is a magnetic guide tip:

[0012] The angle of the magnetic guide tip is 30°-60°, and the extracranial module is further provided with an external magnetic field navigation module in cooperation with the magnetic guide tip.

[0013] Preferably, the microprobe is further provided with a catheter into which a guide core is inserted, the guide core being made of rigid material including any one of titanium alloy or nickel-titanium memory alloy;

[0014] The surface of the guide core is coated with a hydrophilic lubricating coating, and the thickness of the coating is 1-5 microns.

[0015] Preferably, the liquid supply pipe is made of rubber material.

[0016] Preferably, the liquid supply pipe is further sleeved with a degradable stent, and the degradable stent is made of degradable thermoplastic polyester.

[0017] The surface of the degradable stent is preloaded with a drug coating, and the degradable stent is a hollow tubular stent, the inner wall of which is attached to the liquid supply pipe and the microprobe, the liquid supply pipe and the microprobe are magnetically sealed, the separation force is greater than or equal to 3 N, and the leakage rate is less than 0.05 microliters per minute.

[0018] Preferably, the control pump is a morphine pump.

[0019] Another aspect of the present application discloses a method for using an extracranial implementation of a convection-enhanced delivery device, comprising the following steps:

[0020] S1: generating a target three-dimensional model based on patient image data, and calculating the implantation path of the microprobe;

[0021] S2: implanting the microprobe and positioning it through magnetic navigation;

[0022] S3: connecting the extracranial module with the liquid supply pipe, and positioning the degradable stent with the cranial cavity;

[0023] S4: starting the extracranial module to perform drug convection infusion and drug convection infusion;

[0024] S5: retaining the degradable stent after the operation to gradually hydrolyze, and synchronously releasing the drug from the drug-loaded coating to assist.

[0025] Another aspect of the present application discloses the application of an extracranial implementation of a convection-enhanced delivery device in intracranial treatment.

[0026] Compared with the prior art, the intracranial module (microprobe + degradable stent) and the extracranial module (control pump + liquid supply pipe) in the present application are detachably connected, the volume of the implanted object is reduced, the risk of infection is reduced, the liquid supply channel is magnetically sealed to achieve a leakage-free connection (leakage rate < 0.05 microliters per minute), and the high-pressure infusion requirement is met.

[0027] The stent in the present application is made of degradable thermoplastic polyester, the degradation period matches the treatment period, secondary removal surgery is avoided, the surface is preloaded with a drug coating, and the auxiliary drug is synchronously released during the degradation process of the stent to improve the comprehensive therapeutic effect. Attached Figure Description

[0028] Figure 1 is a schematic diagram of a convection-enhanced delivery device implemented extracranially. Detailed Implementation

[0029] The present invention will now be described in further detail with reference to the accompanying drawings.

[0030] As shown in Figure 1, an extracranial convection-enhanced delivery device includes an intracranial module and an extracranial module.

[0031] The extracranial module is connected to the intracranial module, and a fluid supply channel is formed between the extracranial module and the intracranial module.

[0032] In one embodiment:

[0033] The intracranial module includes a microprobe that can be inserted into target tissue. The distal end of the microprobe also has an anatomically compatible sharp penetrating end. The extracranial module includes a control pump and a supply tube connected thereto. The supply tube is sealed to the proximal end of the microprobe for delivering drug-containing fluid to the microprobe. An anti-backflow component is also provided between the supply tube and the control pump.

[0034] More specifically, the sharp penetrating end structure is either a conical spiral structure or a magnetically guided tip;

[0035] When the sharp penetrating end structure is a magnetically guided tip:

[0036] The magnetic guide tip has an angle of 30° to 60°, and the extracranial module is also equipped with an external magnetic field navigation module in conjunction with the magnetic guide tip to facilitate guidance operations.

[0037] In one embodiment:

[0038] The microprobe also has a conduit into which a guide core can be inserted. The guide core is made of a rigid material, including either titanium alloy or nickel-titanium shape memory alloy.

[0039] The surface of the conductor is coated with a hydrophilic lubricating coating with a thickness of 1–5 μm.

[0040] In one embodiment:

[0041] The liquid supply tube is made of rubber, and a biodegradable support is also fitted over the liquid supply tube. The biodegradable support is made of biodegradable thermoplastic polyester.

[0042] The biodegradable stent is pre-loaded with a drug coating on its surface. The biodegradable stent is a hollow tubular stent with its inner wall in contact with the liquid supply tube and the microprobe. The liquid supply tube and the microprobe are magnetically sealed. The separation force is ≥3 N, the leakage rate is <0.05 μL / min, and the control pump is a morphine pump that can be used in multiple modes.

[0043] In specific use:

[0044] Comprising the following steps:

[0045] S1: generating a target three-dimensional model based on patient image data, calculating the implantation path of the microprobe;

[0046] S2: microprobe implantation and positioning by magnetic navigation;

[0047] S3: docking the extracranial module with the liquid supply pipe, positioning the cranial cavity through the degradable stent;

[0048] S4: starting the extracranial module for drug countercurrent infusion and drug countercurrent infusion;

[0049] S5: retaining the degradable stent after surgery to gradually hydrolyze, and synchronously releasing the drug-loaded coating to assist.

[0050] In specific implementation,

[0051] Based on patient MRI data to reconstruct a target three-dimensional model, plan the implantation path of the microprobe, insert the titanium alloy guide core (coating thickness 3 μm) into the microprobe catheter, pre-bend to the target angle, the outer wall of the liquid supply pipe (rubber material) is sleeved with a PLA degradable stent, and the microprobe is inserted through the skull micro-hole (diameter 1.5 mm), the external magnetic field navigation module (gradient magnetic field strength 1.5 T / m) is started, and the magnetic guide tip (angle 45°) is guided to reach the target area, at this time the guide core is extracted, and the liquid supply pipe is connected through magnetic sealing;

[0052] The pump is set to pulse or constant pressure mode (reference pressure 250 mmHg, frequency 2 Hz) to infuse the drug solution while monitoring the release rate of the stent drug-loaded coating, in use, the core area drug concentration reaches more than 95%, and the stent degradation rate is >90% after 30 days.

[0053] In another embodiment,

[0054] A conical spiral tip microprobe (pitch 1 mm) is used, and a nickel-titanium guide core is used to assist in rotating puncture. The rotation puncture generates a tissue gap, reducing the infusion resistance. After connecting the liquid supply pipe, the drug solution is infused in constant pressure mode or pulse mode, and the degradable stent is preloaded with other drugs.

[0055] The control pump (morphine pump) provides two infusion modes:

[0056] Constant pressure mode: stable pressure (50-300 mmHg), suitable for shallow target areas;

[0057] Pulse mode: periodic pressure fluctuation (reference pressure ±15%, frequency 1-3 Hz), for deep lesions.

[0058] Anti-reflux assembly: including between the liquid supply pipe and the control pump, using double check valve + elastic diaphragm structure, when positive infusion, elastic diaphragm opens, when pressure drops, diaphragm closes instantly.

[0059] The liquid supply pipe uses rubber / PU material, the inner diameter is 0.5-1.2 mm, and the microprobe guide pipe is coated with an albumin adsorption layer on the inner wall.

[0060] When the magnetic sealing is used, the distal end of the liquid supply pipe is connected with the soft iron magnetic ring at the proximal end of the microprobe through the neodymium-iron-boron magnetic ring (surface plated with gold).

[0061] The contents not described in detail in the specification belong to the prior art known to those skilled in the art.

[0062] In the present application, the terms "first", "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first", "second" can explicitly or implicitly include one or more of the features. In the description of the present application, the meaning of "a plurality of" is two or more, unless otherwise explicitly specified and limited.

[0063] In the present application, unless otherwise explicitly specified and limited, the terms "mounting", "connecting", "connecting", "fixing" and the like should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or it can be integrated; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the internal communication of two elements or the interaction relationship between two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0064] The above describes the present application and its embodiments, which is not restrictive, and the shown in the drawings is only one of the embodiments of the present application, and the actual structure is not limited thereto. In general, if those skilled in the art are inspired, without departing from the purpose of the present application, without creative design, similar structure and embodiments of the technical scheme can be designed, which should belong to the protection scope of the present application.

Claims

1. An extracranially implemented convection-enhanced delivery device, characterized by: The device comprises an intracranial module and an extracranial module. The extracranial module is connected with the intracranial module, and a liquid supply channel is formed between the extracranial module and the intracranial module.

2. An extracranially implemented convection-enhanced delivery device according to claim 1, wherein: The intracranial module comprises a microprobe (1) which can be inserted into target tissue, and the distal end of the microprobe (1) further has an anatomically compatible sharp penetrating end (2).

3. An extracranially implemented convection-enhanced delivery device according to claim 2, wherein: The extracranial module comprises a control pump (3) and a liquid supply pipe (4) connected therewith, the liquid supply pipe (4) is sealingly connected with the proximal end of the microprobe (1), and is used for delivering a drug-containing fluid to the microprobe (1), and the liquid supply pipe (4) and the control pump (3) are further provided with an anti-reflux assembly (5).

4. An extracranially implemented convection-enhanced delivery device according to claim 2, wherein: The sharp penetrating end (2) has a conical spiral structure or a magnetic guide tip. When the sharp penetrating end (2) has a magnetic guide tip, the magnetic guide tip has an angle of 30°-60°, and the extracranial module is further provided with an external magnetic field navigation module matched with the magnetic guide tip. The microprobe (1) is further provided with a catheter into which a guide core (6) can be inserted, and the guide core (6) is made of rigid material including any one of titanium alloy or nickel-titanium memory alloy.

5. An extracranially implemented convective enhancement delivery device according to claim 2, wherein: The surface of the guide core (6) is coated with a hydrophilic lubricating coating, and the coating has a thickness of 1-5 μm. The liquid supply pipe (4) is made of rubber material.

6. An extracranially implemented convective enhancement delivery device according to claim 3, wherein: The liquid supply pipe (4) is further sleeved with a degradable stent (7), and the degradable stent (7) is made of degradable thermoplastic polyester.

7. An extracranially implemented convective enhancement delivery device according to claim 3, wherein: The surface of the degradable stent (7) is preloaded with a drug coating, the degradable stent (7) is a hollow tubular stent, the inner wall of which is attached to the liquid supply pipe (4) and the microprobe (1), the liquid supply pipe (4) and the microprobe (1) are magnetically sealed, the separation force is ≥3 N, and the leakage rate is <0.05 μL / min. The control pump (3) is a morphine pump.

8. An extracranially implemented convective enhancement delivery device according to claim 3, wherein: The device of any one of claims 1-8 is applied, comprising the following steps:

9. A method of using an extracranially implemented convection-enhanced delivery device, comprising: S1: generating a target three-dimensional model based on patient image data, and calculating an implantation path of the microprobe (1); S2: implanting the microprobe (1) and positioning by magnetic navigation; S3: docking the extracranial module with the liquid supply pipe (4), and positioning the degradable stent (7) with the cranial cavity; S4: starting the extracranial module to perform drug countercurrent infusion and drug countercurrent infusion; S5: retaining the degradable stent (7) after the operation to gradually hydrolyze, and synchronously releasing the drug in the drug coating to assist.

10. The application of the extracranial countercurrent enhanced delivery device of any one of claims 1-8 in intracranial treatment. ​