Drug-loaded microparticles, catheter and implant system having the same

Abstract

The application discloses a drug-loaded micro-particle, which comprises a biodegradable shell (31) and a drug-loaded part (34) in the shell, the drug-loaded part (34) contains drugs and is used for being implanted into a tissue in a body through a puncture needle (5), the shell is closed and is designed to form an opening penetrating through the wall thickness of the shell according to a predetermined time. The drug-loaded micro-particle provided by the embodiment of the application has a large size and can be directly implanted into the tissue in the body without needing to pass through a blood vessel. Moreover, the drug-loaded micro-particles with different drugs can be implanted through one-time puncture of the needle, so that the different drugs can promote each other and improve the curative effect. The application can also realize that different drug-loaded micro-particles have different drug release speed curves, and in combination with the technical means that a plurality of drug-loaded micro-particles with different drug release speed curves are implanted at one time, precise control of drug release can be realized.

Description

Technical Field

[0001] This invention relates to a drug-loaded microparticle (hereinafter referred to as microparticle), as well as a catheter and implantation system having the drug-loaded microparticle, belonging to the field of medical interventional device technology. Background Technology

[0002] With the increasing prevalence of interventional procedures, microsphere technology has made significant progress. For example, Hengrui Medicine's subsidiary, Jialisheng, has developed CalliSpheres drug-loaded embolization microspheres and 8Spheres conformal embolization microspheres. Drug-loaded microspheres can be divided into biodegradable types (gelatin microspheres, biodegradable starch microspheres, sodium alginate microspheres) and non-biodegradable types (polyvinyl alcohol modified microspheres, polyvinyl alcohol, sodium acrylate copolymer microspheres).

[0003] Microsphere interventional surgery typically involves injecting drug-loaded microspheres into a vein via a catheter. The blood in the vein propels the microspheres throughout the body, achieving systemic drug delivery.

[0004] In cancer treatment, microspheres are delivered to the tumor tissue via microcatheters through the tumor's blood supply arteries, primarily for treating tumors or lesions with rich blood supply. However, for tumors with poor blood supply, or those supplied by small, multi-branched collateral vessels after multiple interventional treatments, the delivery of microspheres via vascular pathways is limited or fails.

[0005] In addition, there are often various arteriovenous fistulas inside tumors. In this case, microspheres delivered via the arterial route not only fail to stay in the tumor and play a therapeutic role as designed, but also leak out into the veins through the fistula and eventually reach the lungs, causing serious consequences. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a drug-loaded microparticle, as well as a catheter having the drug-loaded microparticle and an implantation system for implanting the drug-loaded microparticle.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] According to a first aspect of the present invention, a drug-loaded microparticle is provided, comprising a biodegradable outer shell 31 and a drug-loaded portion 34 inside the outer shell, for implantation into tissue via a puncture needle 5, wherein:

[0009] The drug-carrying portion 34 contains a drug;

[0010] The outer shell is closed and is designed to form an opening through the thickness of the outer shell wall at predetermined intervals.

[0011] Preferably, the outer casing 31 has at least one slot 33, which does not penetrate the wall thickness of the outer casing 31.

[0012] The slot 33 is designed to form an opening that extends through the thickness of the outer shell wall at predetermined times.

[0013] Preferably, there are multiple slots 33, and they have different depths or different sizes in the wall thickness direction of the outer shell 31.

[0014] Preferably, there are multiple slots 33, and at least one of them extends through the wall thickness of the outer shell 31 and is filled with a slow-dissolving pore filler.

[0015] Preferably, the outer shell of the drug-loaded microparticle carries a drug, and the drug is different from that of the drug-loaded portion 34.

[0016] According to a second aspect of the present invention, a catheter is provided which contains a plurality of the above-described drug-loaded microparticles.

[0017] Preferably, the catheter 4 contains a plurality of drug-loaded microparticles 3, and the plurality of drug-loaded microparticles 3 contain different drugs.

[0018] Preferably, the catheter 4 contains a plurality of drug-loaded microparticles 3, and the plurality of drug-loaded microparticles 3 have different pore surface areas.

[0019] Preferably, the catheter 4 contains a plurality of drug-loaded microparticles 3, and the drug-loaded microparticles 3 located at both ends of the catheter 4 contain contrast agents or radioactive particles.

[0020] Preferably, the catheter 4 contains a plurality of drug-loaded microparticles 3, and the plurality of drug-loaded microparticles 3 have different groove depths.

[0021] Preferably, the catheter 4 contains a plurality of drug-loaded microparticles 3, and the last drug-loaded microparticle contains a procoagulant drug.

[0022] According to a third aspect of the present invention, an implantation system for implanting drug-loaded microparticles is provided, comprising a puncture needle 5 and a plurality of drug-loaded microparticles that can enter tissues within the body via the puncture needle.

[0023] Preferably, the plurality of said drug-loaded microparticles contain different drugs.

[0024] Preferably, the drug-loaded microparticles have different groove depths or different pore surface areas.

[0025] Preferably, among the plurality of drug-loaded microparticles, the last drug-loaded microparticle contains a procoagulant drug.

[0026] Preferably, in the plurality of drug-loaded microparticles, the first and last two drug-loaded microparticles each carry a contrast agent or radioactive particles.

[0027] The drug-loaded microparticles provided by this invention have a relatively large size, allowing for direct implantation into body tissues without the need for blood vessels. Furthermore, different drug-loaded microparticles can be implanted using a single puncture, enabling different drugs to synergistically enhance therapeutic effects. This invention also allows for the creation of different drug-loaded microparticles with varying drug release rate curves. Combined with the technique of implanting multiple drug-loaded microparticles with different release rate curves in a single procedure, precise control of drug release can be achieved. This invention also changes the manufacturing method of implantable drugs, improving production efficiency. Attached Figure Description

[0028] Figure 1 A schematic diagram of a catheter structure with drug-loaded microparticles provided in an embodiment of the present invention;

[0029] Figure 2 This is a schematic diagram of the structure of drug-loaded microparticles provided in an embodiment of the present invention;

[0030] Figure 3 for Figure 2 The diagram shows the structure of drug-loaded microparticles with different groove depths.

[0031] Figure 4 for Figure 2 The diagram below shows the manufacturing process of drug-loaded microparticles.

[0032] Figure 5 This is a schematic diagram of the drug release rate curve in drug-loaded microparticles;

[0033] Figure 6 To be Figure 1 A schematic diagram illustrating the process of drug-loaded microparticles being pushed into the body. Detailed Implementation

[0034] The technical content of the present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0035] like Figures 1-3 As shown, the drug-loaded microparticles 3 provided in this embodiment of the invention include a shell 31 and a drug-loaded portion 34 housed inside the shell 31. The shell 31 is made of a biodegradable material and may not be drug-loaded; alternatively, it may be made of microspheres or drug-loaded materials to achieve drug loading. The length of the drug-loaded microparticles 3 is in the range of 2–8 mm, particularly greater than 5 mm and less than 7 mm. Drug-loaded microparticles of this size can be fixed in a specific location after being implanted into tissues, continuously releasing the drug.

[0036] like Figure 2 and Figure 3As shown, the outer casing 31 has multiple slots 33 with different depths. At the locations of slots 33 with greater depths, the wall thickness H1 of the outer casing 31 is smaller; at the locations of slots 33 with smaller depths, the wall thickness H2 of the outer casing 31 is greater than H1; and at locations without slots 33, the wall thickness H is greater than H2. Thus, by setting slots 33 of different depths, the wall thickness of the outer casing 31 varies. At locations with smaller wall thicknesses, the outer casing 31 will degrade under the influence of medication, blood, and / or bodily fluids, thus turning the slot into a through-hole. Once a slot becomes a through-hole, blood or bodily fluids from outside the outer casing 31 will enter the interior of the outer casing 31 and come into contact with the drug-carrying portion 34. At this time, the drug contained in the drug-carrying portion 34 is released from the interior of the outer casing 31 to the outside, exerting a therapeutic effect.

[0037] The drug-carrying portion 34 of the drug-loaded microparticle 3 is made of a material capable of carrying drugs and degrading in vivo, and is a conventional drug-loaded material. Furthermore, the drug-carrying portion 34 contains a drug, such as drug-loaded microspheres formed by adsorption, dispersion, or mixing of drugs, drug suspensions, drug gels, radioactive particles, etc. It can also be a liquid or suspension such as an acid-base balance regulating solution, or a sensitizer for tumor treatment. The drug-carrying portion 34 is made of a different material than the outer shell 31, and the drug is fixed inside the drug-loaded microparticles and released from the inside out (i.e., internal adsorption and release). This structure differs from the external adsorption and release method of microspheres, where the drug is adsorbed on the outside of the microspheres and released from the outside.

[0038] like Figure 1 As shown, the drug-loaded microparticle delivery conduit provided in this embodiment of the invention includes a longitudinally elongated tube body 1 and a tube head 2. The tube body 1 is a slender, hollow tubular structure with the same diameter as a puncture needle, and both ends are sealed by the tube head 2, capable of accommodating multiple sequentially arranged drug-loaded microparticles 3. The tube body 1 is made of materials such as plastic, resin, or glass, preferably high-performance polyolefin thermoplastic elastomer (TPE), such as the MT-12051 type TPE material produced by Polymax TPE. The tube head 2 includes a male connector 2A and a female connector 2B, located at both ends of the tube body 1, for sealing / sealing the drug-loaded microparticles 3 within the tube body 1. The tube head 2 is a standard Luer connector. Because one end of the tube body is a male connector 2A and the other end is a female connector 2B, multiple tube bodies 1 can be connected by connecting the male connector of one tube to the female connector of another, thereby increasing the drug dosage (i.e., the drug-loaded microparticles in multiple tube bodies 1 can be continuously supplied).

[0039] The inner diameter of the tube body 1 is preferably the same as the inner diameter of the puncture needle, and slightly larger than the cross-sectional dimension of the outer shell of the drug-loaded microparticles 3. This allows the drug-loaded microparticles 3 to slide freely inside the tube body 1, while also preventing the drug-loaded microparticles 3 from becoming disordered and no longer arranged in sequence inside the tube body 1. Thus, the tube diameter is used to ensure the arrangement of the drug-loaded microparticles 3, thereby controlling the amount of drug within the drug-loaded microparticles.

[0040] The following is in conjunction with the appendix Figure 4 Two methods for manufacturing drug-loaded microparticles 3 are introduced.

[0041] <First method for manufacturing drug-loaded microparticles: Extrusion>

[0042] S1: Prepare the casing material according to the pre-determined specifications.

[0043] Here, thermoplastic drug-controlled release materials such as (lactic-co-glycolic acid) polymer (PLGA) or PLA (polylactic acid, also known as polylactide) can be selected. Radioactive particles can also be added to PLA or PLGA to contain radioactive particles within the shell.

[0044] The equipment parameters for heating and melting PLA or PLGA are set according to the required thickness of the outer shell strip 31A (that is, the thickness of the outer shell 31), for example, 0.1 to 0.3 mm, preferably 0.2 mm.

[0045] S2: Prepare the drug with internal loading.

[0046] Prepare the drug to be encapsulated as a drug delivery unit. This drug, formulated according to the therapeutic requirements, can be a suspension, emulsion, or a mixture of gaseous, liquid, and solid drugs; it can be water-soluble or oil-soluble. Radioactive particles or drug-loaded microspheres, or even poly(isobutyl α-cyanoacrylate) nanoparticles loaded with oligonucleotides, can also be added to the aforementioned drug solution.

[0047] S3: Particles that form encapsulated drugs

[0048] During the extrusion of PLA or PLGA, drugs of various forms are injected into their center, and the drugs are encapsulated using the thermoplastic properties of PLA or PLGA. After cooling, a strip containing the drug is formed. At this point, the liquid drug becomes the drug-carrying portion 34 inside the outer shell 31, and PLA or PLGA becomes the outer shell encapsulating the drug-carrying portion 34.

[0049] S4: Localized thinning of the outer shell

[0050] Using a laser drilling machine, such as the S-UV-5 laser drilling machine from Suzhou Xindewei Co., Ltd., grooves 33 are made into the outer shell strip 31A to form the outer shell strip 31B. The diameter, shape, and distribution of the grooves 33 are predetermined. The grooves 33 are created on the outer shell of the particles formed in step S3 by controlling the laser energy and pulse time. Each particle has at least one groove 33, which does not penetrate the wall thickness of the outer shell 31.

[0051] Multiple slots 33 can also be present on a single particle. These slots 33 have different depths (see reference). Figure 3This process thins the outer shell at slot 33. As the outer shell material gradually degrades under the influence of the drug solution inside and body fluids or blood outside, pores first appear at the thinnest part of the shell wall, allowing the drug solution inside the shell to be released to the outside and exert its effect. As degradation continues, pores also appear at slightly thinner areas, increasing the specific surface area of ​​the pores on the shell surface (the ratio of the surface area of ​​the pores on the shell to the total surface area of ​​the shell at a specific moment), thereby accelerating the drug release rate. Here, due to differences in the number or size of slots, the specific surface area of ​​the pores of the two drug-loaded particles is different at different times during the overall degradation process; these are defined as drug-loaded particles with different specific surface areas of pores.

[0052] These slots 33 also have different apertures or shapes. The preferred shape of the slots 33 is cylindrical, but they can also be trumpet-shaped (the diameter of the slot 33 is larger on the outer diameter of the outer shell 31 and smaller on the inner diameter of the outer shell 31); they can also be elongated, etc. As the outer shell material gradually degrades under the influence of the internal drug solution and external body fluids or blood, the area of ​​the slots 33 exposed from the outer shell changes, which can alter the specific surface area of ​​the drug-loaded particles, thereby changing the drug release rate curve.

[0053] Therefore, by controlling factors such as the number, depth, and size of grooves on the outer shell of the drug-loaded microparticles 3, the specific surface area can be changed, thereby altering the drug release rate curve. In other words, the groove design provided in this embodiment of the invention can be used to control the drug release rate. For example, if the groove depth of the first drug-loaded microparticle is greater than that of the second drug-loaded microparticle (i.e., the wall thickness of the outer shell is thinnest at that location), then the first drug-loaded microparticle will begin releasing the drug first; if the second drug-loaded microparticle has more grooves or a larger groove size than the first drug-loaded microparticle, as degradation progresses, the specific surface area of ​​the openings becomes larger than that of the first drug-loaded microparticle, and its release rate will become faster than that of the first drug-loaded microparticle.

[0054] S5: Heat-sealing into granules

[0055] The shell strip that has been partially thinned is made into granules using a heat sealing machine, resulting in drug-loaded microparticles 3, which contain a drug-loaded part 34.

[0056] In the first manufacturing method, the outer shell of the freshly processed drug-loaded microparticles 3 will not form through holes, but the locally thinned outer shell has a very thin wall (e.g., less than 0.1 mm), which is conducive to rapid degradation after implantation to form through holes.

[0057] <Second method for manufacturing drug-loaded microparticles: heat sealing>

[0058] S11: Prepare the outer casing strip of the pre-ordered specifications.

[0059] like Figure 4As shown, according to the predetermined specifications, outer shell strip 31A is selected and subjected to cleaning, sterilization, and other treatments. The outer shell strip is a strip-shaped tube with one end sealed (closed end 30A) and one end open (open end 30B). In this embodiment, it is a (lactic-co-glycolic acid) polymer (PLGA) or PLA material (polylactic acid, also known as polylactide); polycarbonate, polyamino acid, polyvinyl alcohol, ethyl cellulose (EC), polyethylene, polypropylene, polysiloxane, and polyethylene oxide can also be used.

[0060] The predetermined specifications refer to the fact that the material, size, cross-sectional shape, and other indicators of the outer shell strip are determined in advance. The outer shell strip can be provided by the supplier, and it only needs to be selected according to the predetermined specifications during manufacturing. The thickness of the outer shell strip 31A (that is, the thickness of the outer shell 31) is less than 1 mm, for example, 0.1 to 0.4 mm, and more preferably 0.2 mm.

[0061] The cross-section of the outer shell strip 31A can be various shapes, such as circular, hexagonal, pentagonal, or elliptical. In the longitudinal direction, the cross-section of the outer shell strip 31A can vary; for example, one end of the outer shell strip can be a large-diameter circle, and the other end a small-diameter circle. The specific shape of the outer shell strip 31A is determined by the drug loading capacity of the outer shell 31, the drug loading capacity of the drug-carrying section 34, and the selected manufacturing process.

[0062] The grooves for drug-loaded microparticles can also be filled with water-soluble, slow-dissolving pore fillers. After the microparticles are implanted in the body, the drug can only be released from the grooves after the filler dissolves, thus achieving delayed release.

[0063] S12: Loading the outer shell strip with the drug.

[0064] The drug solution is injected through the open end 30B of the strip-shaped outer shell, and then the open end is sealed. The injected drug solution is a pre-mixed drug according to the treatment requirements, and can be a suspension, emulsion, etc. The first manufacturing method uses a gelatin solution, for example, 50-200 mg of gelatin solution and 10-20 mg of cisplatin (for hepatic artery chemoembolization). It can also be radioactive particles or drug-loaded microspheres, or even poly(isobutyl α-cyanoacrylate) (PIBCA) nanoparticles loaded with oligonucleotides.

[0065] S13: Laser grooving of the outer casing strip

[0066] Using a laser drilling machine, such as the S-UV-5 laser drilling machine from Suzhou Xindewei Co., Ltd., grooves 33 are made into the outer shell strip 31A to form the outer shell strip 31B. The size, shape, and distribution of the grooves 33 are predetermined. By controlling the laser energy and pulse time, grooves 33 are created on the outer shell of the particles formed in step S1. It is ensured that each particle has at least one groove 33 that does not penetrate the wall thickness of the outer shell 31. As mentioned above, a particle can also have multiple grooves 33, with different depths, shapes, and sizes, forming an opening that penetrates the outer shell wall thickness.

[0067] S14: Vacuum freeze drying

[0068] Depending on the type of drug solution, different freeze-drying processes can be employed. Taking gelatin solution as an example, it is kept in a low-temperature vacuum device at a temperature of (-60 to -50)℃ for (6 to 10) hours, then removed to freeze-dry the gelatin solution into gelatin particles. Alternatively, it can be kept in a low-temperature vacuum device at (-30 to -40)℃ for (20 to 30) hours. After vacuum freeze-drying, the drug solution becomes the drug-carrying portion 34.

[0069] S15: Heat-sealing granulation

[0070] Using a heat-sealing machine, the outer shell strip, which has been partially thinned and whose internal liquid medicine has been dried into a solid state, can be heat-sealed into particles of a predetermined length, i.e. drug-loaded microparticles, which are loaded with medicine inside.

[0071] The drug-loaded microparticles 3 formed through the aforementioned steps can have various specifications, and even if the external dimensions of the drug-loaded microparticles 3 are the same, they can still have different drug loading capacities. Among them, the drug-loaded microparticles of type A have a large drug loading capacity on the outer shell 31, that is, the volume of the outer shell 31 is large, and its wall thickness and / or size of the outer shell 31 is large; the drug-loaded microparticles of type B have a large drug loading capacity in the drug-loading part 34 (for example, some drugs are not suitable for drug loading with an outer shell, so the drug loading capacity of the drug-loading part 34 can only be increased), and its outer shell wall thickness is smaller than that of the drug-loaded microparticles of type A. While keeping the outer shell size unchanged, it can accommodate more drug-loading parts 34 than the drug-loaded microparticles of type A; the drug-loaded microparticles of type C have the same size as the drug-loaded microparticles of type A, but the material of their drug-loading parts 34 is different. The drug loading rate of the drug-loading part 34 material of the drug-loaded microparticles of type C is greater than that of the drug-loaded microparticles of type A.

[0072] <Third method for manufacturing drug-loaded microparticles: Filling method>

[0073] S21: Prepare the outer casing strip of the pre-ordered specifications.

[0074] Refer to step S11 in the second method, but the outer shell strip is closed at both ends.

[0075] S22: Laser grooving of the outer casing strip

[0076] Refer to step 13, but in this step, a slot with a wall thickness that penetrates at least one shell strip is formed, as well as multiple slots with wall thicknesses that do not penetrate the shell strip (ensuring that each particle has at least one slot with a wall thickness that does not penetrate the shell strip).

[0077] S23: Loading the outer shell strip with the drug.

[0078] Referring to step 12, liquid medication is injected into the interior of the outer shell strip through a groove formed in step 22 that extends through the wall thickness of the outer shell strip. Gelatin-based medication is preferred.

[0079] S24: Vacuum freeze drying (refer to step 14)

[0080] S25: A slot that fills the entire thickness of the outer casing wall.

[0081] The slots penetrating the outer shell wall are filled with a slow-dissolving pore filler, preventing drug leakage from the shell strip. Furthermore, the filler is a water-soluble material that degrades faster than the shell. After these drug-loaded microparticles are implanted, the drug can only be released from the shell after the filler dissolves and the slots are exposed, thus achieving the purpose of delayed release.

[0082] S26: Heat sealing into granules (refer to step 15)

[0083] The drug-loaded microparticles 3 produced in the aforementioned steps can then be used to externally load drugs onto the outer shell. This is because the material of the outer shell 31 itself is also a drug-loadable material.

[0084] Regardless of the method used to prepare the drug-loaded microparticles, they can be encapsulated in a catheter for sealed storage. Multiple drug-loaded microparticles can be sequentially delivered into the catheter via airflow, ensuring not only sealed storage but also convenient implantation.

[0085] For example Figure 1 and Figure 5 As shown, the same tube 1 contains 6 drug-loaded microparticles, including a first drug-loaded microparticle containing an anticancer drug in a shell. Figure 5 (As shown by the double-dotted dashed line); a second drug-carrying microparticle containing anticancer drugs with a large groove depth (as shown by the double-dotted dashed line); Figure 5 (shown by the solid line); there is also a third drug-loaded microparticle containing an anticancer drug sensitizer and having the largest open-pore specific surface area (as shown by the solid line); Figure 5(As shown by the dashed line), the two fourth drug-loaded microparticles at both ends contain radioactive particles. First, the first drug-loaded microparticle, with its outer shell, begins releasing the drug upon implantation. Then, the second drug-loaded microparticle, with its deeper groove, begins releasing the drug within a short time. After the first and second drug-loaded microparticles have released for a period of time, the fourth drug-loaded microparticles begin releasing the drug, and the release rate accelerates as the degree of degradation increases and the specific surface area of ​​the pores increases. The radioactive particles at both ends can be visualized using imaging techniques to show the location of all particles in this injection.

[0086] Optionally, one type of drug-loaded microparticle can be contained inside the tube body 1 of one catheter, while another type of drug-loaded microparticle can be contained inside the tube body 1 of another catheter. Different catheters can be selected for each treatment session, or different catheters can be connected in a single treatment to obtain different quantities of different types of drug-loaded microparticles. By introducing drug-loaded microparticles with different release rate curves, the release time can be extended, for example, from 20 days to 27 days or even 30 days; or an ideal release curve can be obtained. Therefore, this invention has the advantages of convenient compatibility and precise control of drug release rate.

[0087] like Figure 6 As shown, during the implantation surgery, the Luer interface of the tube head 2 at one end of the tube body 1 provided in this embodiment of the invention is connected to the puncture needle. The drug-loaded microparticles inside the tube body 1 are pushed into the puncture needle along the catheter using a pusher. The drug-loaded microparticles are then pushed into the body tissue using the puncture needle core 6 (flat-headed pusher). Using a contrast agent, the radioactive particles (or contrast agents containing iodine, barium, tantalum, etc.) contained in the drug-loaded portion 34 of the microparticles will reveal the location of the microparticles, thereby guiding the surgeon during the implantation procedure. For example, anhydrous ethanol in the drug-loaded microparticles may be directly released into the tissue. Since the outer shell 31 of the drug-loaded microparticles is a biodegradable material, it will degrade into non-toxic and harmless substances such as water and carbon dioxide after a certain period of time (this is a pre-designed time). The gelatin, as the drug carrier, will also degrade rapidly in the body. Therefore, the drug-loaded microparticles provided in this embodiment of the invention can simultaneously carry multiple drugs and can be completely degraded in the body without causing toxic side effects.

[0088] A more optimized approach involves implanting multiple drug-loaded microparticles into the puncture needle at once, with the last microparticle carrying a procoagulant. After implantation, this last microparticle is inserted into the puncture needle tract. This serves two purposes: firstly, it refills the tract, providing physical pressure for hemostasis; secondly, the procoagulant is released within the tract, achieving local hemostasis. It can also carry antibiotics, which are released within the tract to prevent infection. Therefore, this invention can prevent complications such as bleeding from the puncture needle tract.

[0089] The drug-loaded microparticles provided in this invention have a relatively large size, allowing for direct implantation into body tissues without the need for blood vessels. Furthermore, drug-loaded microparticles carrying different drugs can be implanted in a single puncture, enabling different drugs to synergistically enhance therapeutic efficacy. This invention also allows for the creation of different drug-loaded microparticles with varying drug release rate curves. Combined with the technique of implanting multiple drug-loaded microparticles with different release rate curves in a single procedure, precise control of drug release is achieved. Using the technical solution provided by this invention, drug release rate curves can be designed via computer programming, and laser grooving or the selection of slow-dissolving pore-filling agents can be used to create pores in each drug-loaded microparticle according to a set time (converting non-through grooves into through ones) and to change the specific surface area of ​​the pores. This ensures that the drug within the drug-loaded microparticles is released according to the ideal release rate curve, thereby improving controlled-release precision and therapeutic effect. Using the technical solution provided by this invention, a drug release rate curve can be designed by computer programming, and the laser opening can be controlled accordingly to change the specific surface area of ​​the opening. Then, a slow-dissolving pore filler is selected so that each drug-loaded microparticle opens a hole according to a set time (the non-through groove becomes through), so that the drug in the drug-loaded microparticle is released according to the ideal release rate curve, thereby improving the controlled release accuracy and therapeutic effect. This improves the manufacturing method of implantable drugs and can improve production efficiency while improving drug efficacy.

[0090] The foregoing has provided a detailed description of the drug-loaded microparticles, the catheter containing the drug-loaded microparticles, and the implantation system provided by this invention. Any obvious modifications made by those skilled in the art without departing from the essence of this invention will constitute an infringement of the patent rights and will incur corresponding legal liability.

Claims

1. A drug-loaded microparticle comprising a biodegradable outer shell (31) and a drug-loaded portion (34) within the outer shell, for implantation and fixation in in vivo tissue via a puncture needle (5), characterized in that: The drug-carrying portion (34) contains a drug, the outer shell is closed and has an opening designed to form through the wall thickness of the outer shell at predetermined intervals to allow the drug to be released from the outer shell (31) and to control the release rate of the drug. The drug-carrying portion (34) is any one of drug-carrying microspheres, drug gels, or drug suspensions. The outer shell (31) has at least one slot (33) with different depths or different sizes in the wall thickness direction of the outer shell (31) to change the specific surface area.

2. The drug-loaded microparticles as described in claim 1, characterized in that: The slot (33) does not penetrate the wall thickness of the outer shell (31). The slot (33) is designed to form an opening that penetrates the wall thickness of the outer shell at a predetermined time to change the specific surface area.

3. The drug-loaded microparticles as described in claim 1, characterized in that: The slots (33) are multiple, and at least one of them extends through the wall thickness of the outer shell (31) and is filled with a slow-dissolving pore filler.

4. The drug-loaded microparticles as described in claim 2, characterized in that: The outer shell of the drug-carrying microparticle carries a drug, which is different from the drug-carrying part (34).

5. A catheter having a plurality of drug-loaded microparticles as described in any one of claims 1 to 4 contained therein.

6. The catheter as described in claim 5, characterized in that: The catheter contains multiple drug-loaded microparticles (3), and the multiple drug-loaded microparticles (3) contain different drugs.

7. The catheter as described in claim 5 or 6, characterized in that: The catheter contains multiple drug-loaded microparticles (3), and the multiple drug-loaded microparticles (3) have different pore surface areas.

8. The catheter as described in claim 5 or 6, characterized in that: The catheter contains multiple drug-loaded microparticles (3), and the drug-loaded microparticles (3) located at both ends of the catheter contain contrast agents or radioactive particles.

9. The catheter as described in claim 5 or 6, characterized in that: The catheter contains a plurality of drug-loaded microparticles (3), and the plurality of drug-loaded microparticles (3) have different groove depths.

10. The catheter as described in claim 5 or 6, characterized in that: The catheter contains multiple drug-loaded microparticles (3), and the last of these microparticles contains a procoagulant drug.

11. An implantation system for implanting drug-loaded microparticles, comprising a puncture needle (5), characterized in that... It also includes a plurality of drug-loaded microparticles that can enter the body tissues through the puncture needle; wherein the drug-loaded microparticles are the drug-loaded microparticles according to any one of claims 1 to 4.

12. The implantation system as claimed in claim 11, characterized in that: The multiple drug-loaded microparticles contain different drugs.

13. The implantation system as described in claim 12, characterized in that: The drug-loaded microparticles have different groove depths or different pore surface areas.

14. The implantation system as described in claim 12, characterized in that: Of the plurality of drug-loaded microparticles, the last drug-loaded microparticle contains a procoagulant drug.

15. The implantation system according to any one of claims 11 to 14, characterized in that: In the plurality of drug-loaded microparticles, the first and last two drug-loaded microparticles are loaded with contrast agent or radioactive particles.

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