Anti-tumor degradable prostate stent containing traditional Chinese medicine sustained-release agent and preparation method of anti-tumor degradable prostate stent

Abstract

The invention provides an anti-tumor degradable prostate stent containing a traditional Chinese medicine sustained-release agent and a preparation method of the anti-tumor degradable prostate stent, the anti-tumor degradable prostate stent has tumor microenvironment response and targeted therapy effects, and the anti-tumor degradable prostate stent containing the traditional Chinese medicine sustained-release agent comprises a degradable prostate stent body; the sustained-release layer is formed on the surface of the degradable prostate stent body, the sustained-release layer contains a carrier, a connecting agent and an anti-tumor drug active component carried by the carrier, the carrier is a nano-porous material, the nano-porous material comprises a prostate cancer cell membrane, the anti-tumor drug active component contains a traditional Chinese medicine monomer, and the anti-tumor drug active component contains an anti-tumor drug. The traditional Chinese medicine monomer is one or more of licochalcone, ginsenoside, curcumin, ganoderan, tanshinone IIA and dendrobine. According to the anti-tumor degradable prostate stent containing the traditional Chinese medicine sustained-release agent, a patient does not need to be subjected to secondary surgical removal after implantation, and responsive drug release and drug targeted therapy can be achieved.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical engineering, and in particular to an anti-tumor degradable prostate stent containing a traditional Chinese medicine sustained-release agent and a preparation method thereof. Background Art

[0002] Prostate cancer is one of the most common malignant tumors in men worldwide, with a huge number of new cases each year. Currently, radical prostatectomy is listed as the first-line treatment option, but the recurrence rate after surgery is still high.

[0003] In addition, during radical prostatectomy, medical staff usually need to cut off the end of the patient's catheter to ensure that the operation goes smoothly. After the resection, the patient needs to implant a new catheter to maintain urination function. However, the currently widely used plastic catheters need to be removed in a second operation 2 to 3 weeks after implantation, which not only increases the patient's physical burden, but also increases the risk of complications such as infection with multiple surgeries. It also reduces the overall treatment experience and affects the patient's quality of life after surgery. Summary of the invention

[0004] In view of this, the present invention provides an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent. After implantation, the patient does not need to undergo a secondary surgery to remove it, thereby reducing the risk of complications such as infection, alleviating the patient's physical burden, and improving the treatment experience and postoperative quality of life.

[0005] The present invention also provides a method for preparing an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent.

[0006] In order to solve at least one of the above technical problems, the present invention adopts the following technical solutions:

[0007] The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to the first embodiment of the present invention comprises:

[0008] Degradable prostate stent body;

[0009] The sustained-release layer is formed on the surface of the degradable prostate stent body. The sustained-release layer contains a carrier, a connector, and an active ingredient of the anti-tumor drug carried by the carrier.

[0010] The carrier is a nanoporous material, the nanoporous material includes a prostate cancer cell membrane, and the linker is one or more of hyaluronic acid, polytrimethylene carbonate, polyvinyl alcohol, gelatin, chitosan, cellulose, polyacrylamide, poly-N-isopropylacrylamide, polyvinyl pyrrolidone, and poly(hydroxyethyl methacrylate) modified with hydroxyl or thiol groups;

[0011] The active ingredients of the anti-tumor drug contain Chinese medicine monomers, which are one or more of licorice chalcone, ginsenoside, curcumin, ganoderma lucidum polysaccharide, tanshinone IIA, and dendrobium alkaloids.

[0012] Furthermore, the active ingredients of the anti-tumor drug also contain at least one or more of enzalutamide, abiraterone, megestrol acetate, flutamide and its derivatives, bicalutamide, carboplatin, cisplatin, and etoposide.

[0013] Furthermore, the nanoporous material also includes one or more of plant vesicles, bacterial vesicles, metal-polyphenol copolymers, micelles formed by cationic surfactants, metal-organic frameworks, and covalent-organic frameworks.

[0014] Furthermore, the surface of the degradable prostate stent body is treated by electrochemical polishing, and the degradable prostate stent further comprises:

[0015] The passivation layer is arranged on the surface of the degradable prostate stent body after electrochemical polishing, wherein the sustained-release layer is arranged on the surface of the passivation layer away from the degradable prostate stent body.

[0016] Furthermore, the passivation layer is one or more of a magnesium fluoride layer, a polydioxanone layer, or an alkalized hydroxide layer.

[0017] Furthermore, the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent also includes:

[0018] The middle layer is arranged between the passivation layer and the sustained-release layer, and is a polydopamine material layer.

[0019] Furthermore, the thickness of the polydopamine material layer is 1 to 5 μm.

[0020] The method for preparing an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the second aspect of the present invention comprises the following steps:

[0021] Step S1, providing a degradable prostate stent body;

[0022] Step S2, providing an anti-tumor drug slurry, wherein the anti-tumor drug slurry contains a carrier, a linker, and an anti-tumor drug active ingredient, wherein the anti-tumor drug active ingredient is connected to the surface of the carrier by the linker,

[0023] The carrier is a nanoporous material, the nanoporous material includes a prostate cancer cell membrane, and the linker is one or more of hyaluronic acid, polytrimethylene carbonate, polyvinyl alcohol, gelatin, chitosan, cellulose, polyacrylamide, poly-N-isopropylacrylamide, polyvinyl pyrrolidone, and poly(hydroxyethyl methacrylate) modified with hydroxyl or thiol groups;

[0024] The active ingredients of the anti-tumor drug contain Chinese medicine monomers, which are one or more of licorice chalcone, ginsenoside, curcumin, ganoderma lucidum polysaccharide, tanshinone IIA, and dendrobium alkaloids;

[0025] Step S3, immersing the degradable prostate stent body in the anti-tumor drug slurry to form a sustained-release layer on the surface of the degradable prostate stent body, thereby obtaining an anti-tumor degradable prostate stent containing a traditional Chinese medicine sustained-release agent.

[0026] Furthermore, in step S3, before immersing the degradable prostate stent body in the anti-tumor drug slurry, the degradable prostate stent body is pretreated, wherein the pretreatment includes:

[0027] The surface of the biodegradable prostate stent body is subjected to electrochemical polishing treatment;

[0028] The surface of the degradable prostate stent body is passivated to form a passivation layer on the surface of the degradable prostate stent body.

[0029] Further, the passivation treatment includes:

[0030] The degradable prostate stent body is immersed in a hydrofluoric acid or sodium fluoride solution to form a magnesium fluoride layer on the surface of the degradable prostate stent body.

[0031] Alternatively, a polydioxanone layer or an alkalized hydroxide layer is coated on the surface of the degradable prostate stent body.

[0032] Furthermore, the preprocessing also includes:

[0033] providing a polydopamine dispersion;

[0034] The degradable prostate stent body is immersed in a polydopamine dispersion to form a polydopamine material layer on the passivation layer on the surface of the degradable prostate stent body.

[0035] The above technical solution of the present invention has at least one of the following beneficial effects:

[0036] The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention comprises: a degradable prostate stent body and a sustained-release layer. The sustained-release layer contains a carrier, a linker, and an anti-tumor drug active ingredient carried by the carrier. Among them, the carrier is a nanoporous material, the nanoporous material includes a prostate cancer cell membrane, and the linker is one or more of hyaluronic acid, polytrimethylene carbonate, polyvinyl alcohol, gelatin, chitosan, cellulose, polyacrylamide, poly-N-isopropylacrylamide, polyvinyl pyrrolidone, and polyhydroxyethyl methacrylate modified by hydroxyl or thiol. The anti-tumor drug active ingredient contains a Chinese medicine monomer, and the Chinese medicine monomer is one or more of licorice chalcone, ginsenoside, curcumin, ganoderma lucidum polysaccharide, tanshinone IIA, and dendrobium.

[0037] Therefore, according to the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention, by implanting the degradable prostate stent with a sustained-release layer into the patient's body, on the one hand, the degradable prostate stent body supports the urethra, and can gradually degrade in the patient's body after keeping the urethra unobstructed, avoiding secondary surgery for removal, reducing the risk of complications such as infection, alleviating the patient's physical burden, and improving the treatment experience and postoperative quality of life. On the other hand, the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent provided by the present invention uses hyaluronic acid modified with thiol or hydroxyl as a linker, which can form a good cross-linking effect with the Chinese medicine monomer. The thiol group is a nucleophilic group that can cross-link with the drug through various forces such as covalent bonds, electrostatic forces, and hydrogen bonds, thereby extending the release period of the drug, thereby realizing the tumor cell microenvironment, such as pH, glutathione (GSH) to cleave chemical bonds, and realize the function of drug responsive release.

[0038] In addition, the Chinese medicine monomers wrapped by the prostate cancer cell membrane can bind to the tumor cell surface membrane protein through ligand-receptor binding to achieve drug targeted therapy.

[0039] Furthermore, according to the different stages of the patient's prostate cancer and the patient's actual physical condition, one or more Chinese medicine monomers are selected for combined use, or one or more Chinese medicine monomers are used in combination with one or more Western medicine monomers as active ingredients of anti-tumor drugs. The implanted anti-tumor degradable prostate stent is gradually released into the prostate tissue, which can further improve the treatment effect and reduce the recurrence rate of prostate cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 It is a schematic diagram of an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention;

[0041] Figure 2 Another schematic diagram of an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention;

[0042] Figure 3 It is a schematic diagram of a part of the structure of an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention;

[0043] Figure 4 The relative survival rate bar graphs of 100% extracts of the anti-tumor degradable prostate stents of Examples 1 to 7 of the present invention used for culturing MC3T3-E1 cells for 1 day and 3 days respectively;

[0044] Figure 5 This is a scanning electron microscope image of Example 1 of the present invention;

[0045] Figure 6 This is a scanning electron microscope image of Example 7 of the present invention;

[0046] Figure 7 This is a scanning electron microscope image of Comparative Example 1 of the present invention;

[0047] Figure 8 This is a scanning electron micrograph of the targeting of ginsenosides to PC3 on the prostate cancer cell membrane of Example 1 of the present invention;

[0048] Fig. 9 This is a bar graph showing the relative survival rates of PC3 cells cultured for 1 day and 3 days using 100% extract of the anti-tumor degradable prostate stent of Example 1 of the present invention.

[0049] Reference numerals: 100. Degradable prostate stent body;

[0050] 110. Passivation layer;

[0051] 120. Middle layer;

[0052] 130. Sustained release layer. DETAILED DESCRIPTION

[0053] In order to make the purpose, technical solution and advantages of the embodiment of the present invention clearer, the technical solution of the embodiment of the present invention will be clearly and completely described below in conjunction with the drawings of the embodiment of the present invention. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0054] Unless otherwise defined, the technical terms or scientific terms used in the present invention shall have the usual meanings understood by persons with ordinary skills in the field to which the present invention belongs. The words "first", "second" and similar words used in the present invention do not indicate any order, quantity or importance, but are only used to distinguish different components. Similarly, words such as "one" or "one" do not indicate quantity restrictions, but indicate the existence of at least one. Words such as "connect" or "connected" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Up", "down", "left", "right" and the like are only used to indicate relative positional relationships. When the absolute position of the object being described changes, the relative positional relationship also changes accordingly.

[0055] The following first describes in detail the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention in conjunction with the accompanying drawings.

[0056] It should be noted that the sources of raw materials not mentioned in the present invention may be commercially available or prepared by conventional methods, and the present invention is not limited to this.

[0057] Figure 1 It is a schematic diagram of an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention; Figure 2 Another schematic diagram of an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention; Figure 3 It is a schematic diagram of the partial structure of an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention.

[0058] like Figures 1 to 3 As shown, the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to an embodiment of the present invention may include: a degradable prostate stent body 100 and a sustained-release layer 130 .

[0059] Specifically, if Figure 1 As shown, the anti-tumor degradable prostate stent according to the embodiment of the present invention can directly adopt a commercially available degradable prostate stent body 100, for example, it can be a magnesium-based metal prostate stent body, that is, a magnesium prostate stent body or a magnesium alloy prostate stent body. Therefore, the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to the embodiment of the present invention is implanted into the patient's body by implanting the degradable prostate stent with a sustained-release layer 130, and the degradable prostate stent body 10 supports the urethra, and after keeping the urethra unobstructed, it can gradually degrade in the patient's body, avoiding secondary surgical removal, reducing the risk of complications such as infection, reducing the patient's physical burden, and improving the treatment experience and postoperative quality of life.

[0060] The sustained-release layer 130 is formed on the surface of the degradable prostate stent body 100 , and the sustained-release layer 130 contains a carrier, a linker, and an active ingredient of an anti-tumor drug carried by the carrier.

[0061] Wherein, the carrier is a nanoporous material, and the nanoporous material includes a prostate cancer cell membrane. The nanoporous material is used to carry the active ingredients of anti-tumor drugs, and enhances the loading capacity and targeting of the active ingredients of anti-tumor drugs, and improves the therapeutic effect. In some embodiments of the present invention, a prostate cancer cell membrane is used as a nanoporous material, and the active ingredients of anti-tumor drugs are carried by it. The active ingredients of anti-tumor drugs wrapped by the prostate cancer cell membrane can bind to the tumor cell surface membrane protein by ligand-receptor binding, and achieve drug targeted therapy. The linker is one or more of hyaluronic acid, polytrimethylene carbonate, polyvinyl alcohol, gelatin, chitosan, cellulose, polyacrylamide, poly-N-isopropylacrylamide, polyvinyl pyrrolidone, and polyhydroxyethyl methacrylate modified by hydroxyl or thiol, all of which are biodegradable polymers with good biocompatibility. Preferably, the linker is hyaluronic acid modified by hydroxyl or thiol.

[0062] Hyaluronic acid is a naturally occurring polysaccharide with good biocompatibility and biodegradability and low irritation to human tissue. Through chemical modification, the hydroxyl (-OH) and thiol (-SH) groups on the hyaluronic acid molecules can form covalent bonds with other molecules, thereby connecting the active ingredients of the anti-tumor drug to the surface of the carrier, thereby forming a sustained-release layer 130 on the surface of the degradable prostate stent body 100.

[0063] Specifically, tumor tissue is acidic (pH value is about 6.5-6.8), and the pH value of normal tissue is about 7.4. The slightly acidic environment of the tumor serves as a stimulus for the release of the drug by the responsive sustained-release layer 130. In some embodiments of the present application, the linker can be hyaluronic acid modified with hydroxyl (-OH), which can form a good cross-linking effect with the Chinese medicine monomer, and realize responsive drug release under the slightly acidic conditions of the tumor microenvironment.

[0064] Glutathione (GSH) in tumor cells is higher. In some embodiments of the present application, the linker can be hyaluronic acid modified by sulfhydryl (-SH), and hyaluronic acid modified by sulfhydryl (-SH) has disulfide bond (-SS-). In the tumor microenvironment, a higher concentration of glutathione can rapidly reduce disulfide bonds, causing the drug to fall off from hyaluronic acid, and realizing responsive drug release. In addition, the sulfhydryl group is a nucleophilic group, which can be cross-linked with the drug by a variety of forces such as covalent bonds, electrostatic forces, and hydrogen bonds, extending the release cycle of the drug, so that the tumor cell microenvironment can be realized, such as pH, glutathione (GSH) to chemical bonds Shearing, realizing the function of drug responsive release. Thus, hyaluronic acid modified by sulfhydryl can have a good connection with the carrier, thereby increasing the loading capacity of the drug, and realizing the effect of intelligent release according to the surrounding tumor microenvironment.

[0065] The active ingredients of the anti-tumor drug contain Chinese medicine monomers, which are one or more of licorice chalcone, ginsenoside, curcumin, ganoderma lucidum polysaccharide, tanshinone IIA, and dendrobium alkaloids.

[0066] Specifically, licorice chalcone has anti-proliferative and anti-tumor effects, and can reduce the formation of abnormal proliferative cells, such as prostate hyperplasia or breast hyperplasia, by regulating signal pathways related to cell proliferation. Licorice chalcone can reduce the number of cancer cells by inducing cell cycle arrest and promoting apoptosis of cancer cells, thereby inhibiting the proliferation of various types of cancer cells, including but not limited to bladder cancer, kidney cancer, prostate cancer, breast cancer, liver cancer and lung cancer. Licorice chalcone also has significant anti-inflammatory and antioxidant properties, which can reduce the inflammatory response in the tumor microenvironment and inhibit the development of tumors. Licorice chalcone can reduce the blood supply of tumors by inhibiting angiogenesis, thereby limiting the growth and spread of tumors.

[0067] Ginsenosides have anti-inflammatory, anti-proliferative and tumor apoptosis-inducing effects. They can reduce inflammatory responses in proliferative tissues and inhibit the occurrence and development of pathological hyperplasia, such as breast hyperplasia and prostate hyperplasia. Ginsenosides also induce tumor cell apoptosis by activating apoptosis pathways (e.g., through changes in caspase3 and bax / bcl ratios), and can also inhibit the migration and invasion of cancer cells. In addition, ginsenosides also help enhance the body's immune function, thereby helping to control and eliminate tumor cells.

[0068] Curcumin has multiple biological activities such as anti-inflammatory, antioxidant, and anti-tumor. It can inhibit the regeneration of tumor cells, reduce postoperative inflammatory reactions, and promote tissue repair. Ganoderma lucidum polysaccharides can activate macrophages, improve the body's immunity, inhibit the regeneration of tumor cells by activating the immune system, reduce postoperative inflammatory reactions, and promote tissue repair. Tanshinone IIA can inhibit the proliferation of tumor cells by affecting the cell cycle and inducing apoptosis. It can also inhibit the formation of tumor blood vessels and reduce postoperative inflammatory reactions. Dendrobium alkaloids have antioxidant and anti-inflammatory properties, and can also interfere with the DNA replication and RNA transcription process of tumor cells, thereby inhibiting their proliferation.

[0069] According to some embodiments of the present application, the active ingredient of the anti-tumor drug may also contain a western medicine monomer, such as one or more of enzalutamide, abiraterone, megestrol acetate, flutamide and its derivatives, bicalutamide, carboplatin, cisplatin, and etoposide.

[0070] Enzalutamide is an androgen receptor antagonist used to treat advanced prostate cancer. Abiraterone is also an androgen receptor antagonist, which is used to treat metastatic castration-resistant prostate cancer by inhibiting androgen synthesis. Megestrol acetate is a progestogen drug that inhibits the growth of prostate cancer cells (also known as PC3) by regulating hormone levels and is suitable for the treatment of advanced prostate cancer. Flutamide and its derivatives are also androgen receptor antagonists, which inhibit the growth of prostate cancer cells by organizing androgens to bind to their receptors and are used to treat advanced prostate cancer. Bicalutamide is also an androgen receptor antagonist used to treat early prostate cancer. Carboplatin and cisplatin are both platinum chemotherapy drugs. Carboplatin organizes the division and growth of cancer cells by destroying DNA structure and function, and is used to treat a variety of cancers. Cisplatin organizes DNA replication and transcription processes by binding to DNA to form crosslinks, and is used to treat a variety of cancers. Etoposide is a topoisomerase II inhibitor that inhibits the growth of cancer cells by preventing DNA replication and transcription processes, and is used to treat a variety of cancers. Specifically, it can be selected according to the different stages of prostate cancer in patients and the actual physical condition of the patient.

[0071] In one embodiment of the present invention, according to the different stages of prostate cancer in patients and the actual physical condition of the patients, one or more Chinese medicine monomers are selected for combined use, or one or more Chinese medicine monomers are used in combination with one or more Western medicine monomers as active ingredients of anti-tumor drugs, which are gradually released into the prostate tissue through the implanted anti-tumor degradable prostate stent, which can further improve the treatment effect and reduce the recurrence rate of prostate cancer.

[0072] For example, the Chinese medicine monomers are ginsenosides and licorice chalcone, and the Western medicine monomers are enzalutamide and / or abiraterone. When ginsenosides are used in combination with enzalutamide or abiraterone, the adverse reactions caused by chemotherapy can be reduced, and the anti-inflammatory and anti-proliferative properties of ginsenosides themselves can further inhibit the progression of tumors. At the same time, the combination of licorice chalcone with ginsenosides, abiraterone or enzalutamide can also help reduce the level of inflammation and reduce inflammatory factors in the tumor microenvironment, thereby assisting treatment.

[0073] In some embodiments of the present invention, the nanoporous material may also include one or more of plant vesicles, bacterial vesicles, metal-polyphenol copolymers, micelles formed by cationic surfactants, metal-organic frameworks, and covalent-organic frameworks. One or more of the above materials can be combined with prostate cancer cell membranes to form a composite material to enhance the drug loading capacity and targeting.

[0074] Specifically, the specific ligands on the membrane of prostate cancer cells can bind to the receptors on the surface of tumor cells to achieve targeted drug therapy. The vesicles can be plant vesicles or bacterial vesicles, etc. The vesicles are wrapped by a phospholipid bilayer and can be loaded with drugs. Metal-polyphenol copolymers are formed by self-assembly of metal ions (such as iron ions, aluminum ions, etc.) and polyphenol compounds (such as tannic acid, catechins, etc.) through coordination bonds. They have good stability, controllable porosity, and the pores can carry drug molecules. They have good biocompatibility and are suitable for drug delivery. The micelles formed by cationic surfactants are composed of a hydrophilic head and a hydrophobic tail. The hydrophobic tail forms a cavity inward, and the hydrophobic cavity can be loaded with drugs. Metal-organic frameworks, also known as metal organic framework materials, are called Metal Organic Frameworks in English, or MOF for short. They are organic-inorganic hybrid materials with intramolecular pores formed by self-assembly of organic ligands and inorganic metal ions or clusters through coordination bonds. MOF has a highly ordered porous structure with adjustable pore size and shape. The pores can carry drug molecules. Drugs can be combined with MOF by physical adsorption or chemical bonding. MOF has a high specific surface area and adjustable pores, which can load a large number of drug molecules. By changing the structure of MOF, controlled release of drugs can also be achieved. MOF has a stable structure and can protect drugs from the effects of enzymes in the body. The full name of covalent-organic framework in English is Covalent Organic Framework, referred to as COF. COF is a crystalline porous structure formed by linking organic structural / functional elements with covalent bonds. COF has a highly ordered porous structure with adjustable pore size and shape. The pores can carry drug molecules. Drugs can be combined with COF by physical adsorption or chemical bonding. COF has a high specific surface area and adjustable pores, which can load a large number of drug molecules. By changing the structure of COF, controlled release of drugs can be achieved. COF has a stable structure and can protect drugs from the effects of enzymes in the body.

[0075] Preferably, the nanoporous material is a composite material formed by combining a prostate cancer cell membrane and a metal-organic framework (MOF), or a composite material formed by combining a prostate cancer cell membrane and a covalent-organic framework (COF). Commonly used MOF materials include ZIF-8, MOF-5, etc., and commonly used COF materials include TPPA-COF, etc. For anti-tumor degradable prostate stents, it is necessary to comprehensively consider ligand-receptor binding to achieve targeted drug therapy, and also to consider biocompatibility, drug loading capacity, drug release control ability and stability to ensure that the nanoporous material does not cause immune response or tissue damage, can carry enough drug amount to achieve therapeutic effect and needs to be able to remain stable in the in vivo environment to protect the drug from being degraded. In this regard, the specific ligand on the prostate cancer cell membrane can bind to the receptor on the surface of the tumor cell to achieve targeted drug therapy. MOF and COF have high specific surface area and adjustable pore structure, can load a large amount of drug molecules, and have stable structure and good biocompatibility, and can protect the drug from the influence of enzymes in the body.

[0076] In some embodiments of the present invention, Figures 2 to 3 As shown, the surface of the degradable prostate stent body 100 is treated by electrochemical polishing, and the anti-tumor degradable prostate stent also includes: a passivation layer 110, which is arranged on the surface of the degradable prostate stent body 100 after the electrochemical polishing treatment, wherein the sustained-release layer 130 is arranged on the surface of the passivation layer 110 away from the side of the degradable prostate stent body 100.

[0077] The surface of the degradable prostate stent body 100 can be electrochemically polished to reduce surface roughness, improve biocompatibility, reduce the chance of bacterial attachment, and reduce the risk of infection. The role of the passivation layer 110 is to reduce the corrosion performance of the degradable prostate stent body 100 and reduce the release of hydrogen gas, a degradation product, which makes it difficult for the sustained-release layer 130 to settle and adhere.

[0078] In some embodiments of the present invention, the passivation layer 110 is one or more of a magnesium fluoride layer, a polydioxanone layer, or an alkalized hydroxide layer.

[0079] By fluoriding the surface of the degradable prostate stent body 100, a dense magnesium fluoride film can be formed on the surface of the degradable prostate stent body 100 (such as a magnesium prostate stent), which can effectively prevent oxidation and corrosion of the degradable prostate stent body 100. The fluoridation agent can be hydrofluoric acid or sodium fluoride.

[0080] Polydioxanone is a biodegradable polymer material, which can be coated on the surface of the degradable prostate stent body 100 to form a polydioxanone material layer as a passivation layer 110. The polydioxanone material layer can also prevent the degradable prostate stent body 100 from oxidation and corrosion.

[0081] In addition, by alkalizing the surface of the degradable prostate stent body 100, a hydroxide layer is formed on the surface, which can prevent the degradable prostate stent body 100 from reacting with other substances in the body fluid. All of the above can improve the biocompatibility and stability of the anti-tumor degradable prostate stent body 100.

[0082] In some embodiments of the present invention, Figures 2 to 3 As shown, the anti-tumor degradable prostate stent may further include: an intermediate layer 120, which is disposed between the passivation layer 110 and the sustained-release layer 130, and is a polydopamine material layer. That is, by disposing the intermediate layer 120 between the passivation layer 110 and the sustained-release layer 130, the intermediate layer 120 is a polydopamine material layer, and the polydopamine material layer enhances the adhesion between the passivation layer 110 and the sustained-release layer 130, thereby ensuring the stability and durability of the sustained-release layer 130.

[0083] Polydopamine, whose full name is Polydopamine in English, is abbreviated as PDA. It is a high molecular polymer formed by self-polymerization reaction of dopamine monomers, and has good biocompatibility, antioxidant properties, and strong adhesion. The polydopamine material layer as the middle layer 120 of the anti-tumor degradable prostate stent can enhance the adhesion between the passivation layer 110 and the sustained-release layer 130, ensure that the sustained-release layer 130 is not easy to fall off, and improve the stability of the entire anti-tumor degradable prostate stent structure. The good biocompatibility of polydopamine can also reduce the inflammatory response that may be caused by the anti-tumor degradable prostate stent after implantation in the patient's body, reduce the rejection reaction of the tissue to the anti-tumor degradable prostate stent, and improve the patient's treatment experience. The polydopamine material layer as the middle layer 120 of the anti-tumor degradable prostate stent, the thickness of the polydopamine material layer can also help regulate the degradation rate of the anti-tumor degradable prostate stent to match the treatment needs.

[0084] In some embodiments of the present invention, the thickness of the polydopamine material layer is 1 to 5 μm. The thickness of the polydopamine material layer of 1 to 5 μm is sufficient to provide sufficient adhesion, ensure good adhesion between the sustained-release layer 130 and the passivation layer 110, further ensure the stability and durability of the sustained-release layer 130, and reduce the risk of falling off. At the same time, the thin and uniform polydopamine layer can further improve the biocompatibility of the entire stent, reduce the rejection reaction of the tissue to the stent, and reduce the occurrence of inflammation and other adverse reactions.

[0085] The method for preparing the anti-tumor degradable prostate stent according to the second aspect of the present invention may include the following steps:

[0086] Step S1, providing a degradable prostate stent body 100.

[0087] Specifically, if Figure 1 As shown, the anti-tumor degradable prostate stent according to the embodiment of the present invention can directly adopt a commercially available degradable prostate stent body 100, for example, a magnesium prostate stent body or a magnesium alloy prostate stent body.

[0088] Step S2, providing an anti-tumor drug slurry, wherein the anti-tumor drug slurry contains a carrier, a linker, and an anti-tumor drug active ingredient.

[0089] The anti-tumor drug slurry can be prepared by uniformly dispersing a carrier, a linker, and an active ingredient of the anti-tumor drug in a solvent. There is no particular limitation on the solvent, as long as the carrier, the linker, and the active ingredient of the anti-tumor drug can be uniformly dispersed therein.

[0090] Regarding the specific selection of carriers, linkers, and active ingredients of anti-tumor drugs, their mechanisms of action, etc., reference may be made to the above description of the sustained-release layer 130 , and a detailed description thereof is omitted here.

[0091] In some embodiments, the preparation process of the anti-tumor drug slurry may include:

[0092] providing a prostate cancer cell membrane suspension;

[0093] Providing a metal-organic framework (MOF) solution or a covalent-organic framework (COF) solution, adding an active ingredient of an anti-tumor drug (such as ginsenoside, licorice chalcone, enzalutamide, abiraterone, etc.) into the MOF or COF solution and stirring and mixing;

[0094] The MOF or COF solution carrying the active ingredients of the anti-tumor drug and the prostate cancer cell membrane suspension are extruded at both ends of the membrane extruder to obtain a suspension of the MOF / COF composite material wrapped by the prostate cancer cell membrane;

[0095] Finally, a hyaluronic acid solution modified by hydroxyl or thiol is provided, and a suspension of a MOF / COF composite material wrapped by prostate cancer cell membranes is added to the hyaluronic acid solution modified by hydroxyl or thiol, and the suspension containing the anti-tumor drug active ingredient-hyaluronic acid-prostate cancer cell membrane-MOF composite material or the suspension of the anti-tumor drug active ingredient-hyaluronic acid-prostate cancer cell membrane-COF composite material is uniformly dispersed by stirring to form an anti-tumor drug slurry.

[0096] Here, it should be noted that the hyaluronic acid solution modified with a hydroxyl group or a thiol group can be prepared or purchased commercially. The steps of preparing a thiol-modified hyaluronic acid solution may include: dissolving hyaluronic acid in deionized water to form a hyaluronic acid solution. Add an appropriate amount of a hydroxylating agent, such as epichlorohydrin, and react at room temperature for 2 to 6 hours. After the reaction is completed, the unreacted hydroxylating agent and by-products are removed by dialysis to obtain a hyaluronic acid solution modified with a hydroxyl group. Similarly, hyaluronic acid is dissolved in deionized water to form a hyaluronic acid solution. Add an appropriate amount of a thiolating agent, such as 3-mercaptopropionic acid (3-MPA), add a catalyst and react at room temperature for 2 to 6 hours. After the reaction is completed, the unreacted thiolating agent and by-products are removed by dialysis to obtain a thiol-modified hyaluronic acid solution.

[0097] Step S3, immersing the degradable prostate stent body in the anti-tumor drug slurry to form a sustained-release layer 130 on the surface of the degradable prostate stent body 100, thereby obtaining an anti-tumor degradable prostate stent containing a traditional Chinese medicine sustained-release agent.

[0098] That is to say, after the degradable prostate stent body 100 is immersed in the anti-tumor drug slurry for a predetermined time and then taken out, the solvent components in the anti-tumor drug slurry are removed by volatilization (such as natural volatilization, vacuum volatilization, heating volatilization, etc.), a sustained-release layer 130 can be formed on the surface of the degradable prostate stent body 100. After drying treatment (such as natural drying at room temperature or high-temperature heating drying at 80-120°C, etc.), an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent can be obtained.

[0099] In some embodiments of the present invention, the degradable prostate stent body 100 is immersed in the above-mentioned anti-tumor drug slurry and shaken at a speed of 55 to 65 rpm for 12 to 24 hours to obtain an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent.

[0100] In some embodiments of the present invention, in step S3, before immersing the degradable prostate stent body 100 in the anti-tumor drug slurry, the degradable prostate stent body 100 may be pretreated, wherein the pretreatment includes:

[0101] The surface of the degradable prostate stent body 100 is subjected to electrochemical polishing treatment;

[0102] The surface of the degradable prostate stent body 100 is passivated to form a passivation layer 110 on the surface of the degradable prostate stent body 100 .

[0103] That is to say, the surface of the degradable prostate stent body 100 is electrochemically polished, thereby reducing the surface roughness, improving biocompatibility, reducing the chance of bacterial attachment, and reducing the risk of infection. The function of the passivation layer 110 is to reduce the corrosion performance of the degradable prostate stent body 100 and reduce the release of hydrogen gas, a degradation product, which makes it difficult for the sustained-release layer 130 to settle and adhere.

[0104] In some embodiments of the present invention, the passivation process may include:

[0105] The degradable prostate stent body 100 is immersed in hydrofluoric acid or sodium fluoride solution to form a magnesium fluoride layer on the surface of the degradable prostate stent body 100, or a polydioxanone layer or an alkalized hydroxide layer is coated on the surface of the degradable prostate stent body 100.

[0106] Specifically, in some other embodiments, the degradable prostate stent body 100 is immersed in a hydrofluoric acid or sodium fluoride solution and allowed to stand for 30 to 60 minutes, the concentration of the hydrofluoric acid or sodium fluoride solution is 0.5 to 1 mol / L, and then the degradable prostate stent body 100 is taken out, thoroughly cleaned and dried to obtain a degradable prostate stent body 100 whose surface passivation layer 110 is a magnesium fluoride layer.

[0107] In some other embodiments, the degradable prostate stent body 100 is placed in a high-pressure reactor, and a NaOH solution is added for hydrothermal reaction for 12 to 48 hours, the concentration of the NaOH solution is 0.8 to 1.2 mol / L, and the reaction temperature is 40 to 100° C. Then, the degradable prostate stent body 100 is taken out, cooled, fully cleaned, and dried to obtain a degradable prostate stent body 100 whose surface passivation layer 110 is a hydroxide layer after alkalization treatment.

[0108] In some other embodiments, a polydioxanone solution is provided, the concentration of the polydioxanone solution is 1wt% to 5wt%, and the degradable prostate stent body 100 is immersed in the polydioxanone solution and allowed to stand for 2 to 6 hours. Thereafter, the degradable prostate stent body 100 is taken out, thoroughly cleaned, and dried to obtain a degradable prostate stent body 100 having a surface passivation layer 110 as a polydioxanone layer.

[0109] In some embodiments of the present invention, preprocessing may further include:

[0110] providing a polydopamine dispersion;

[0111] The degradable prostate stent body 100 is immersed in a polydopamine dispersion to form a polydopamine material layer on the passivation layer 110 on the surface of the degradable prostate stent body 100 .

[0112] The polydopamine material layer is used to ensure good adhesion between the sustained-release layer 130 and the passivation layer 110, further ensuring the stability and durability of the sustained-release layer 130 and reducing the risk of falling off. At the same time, the thin and uniform polydopamine layer can further improve the biocompatibility of the entire stent, reduce the reaction of tissues to the stent, and reduce the occurrence of inflammation and other adverse reactions.

[0113] In some other embodiments, the preparation of the polydopamine dispersion is usually prepared by the self-polymerization reaction of dopamine in a weakly alkaline aqueous solution. The self-polymerization reaction can be carried out by an existing conventional method, and the present invention does not specifically limit this. The degradable prostate stent body 100 is immersed in the polydopamine dispersion, kept away from light for 4 to 6 hours, then taken out, fully cleaned and dried to form a polydopamine material layer on the passivation layer 110 on the surface of the degradable prostate stent body 100.

[0114] It should be noted that the degradable prostate stent body 100 can also be directly immersed in the dopamine solution and kept away from light for 12 to 28 hours, during which time the dopamine molecules fully react on the surface of the degradable stent to form a polydopamine material layer.

[0115] The following examples further illustrate the method for preparing the anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent of the present invention.

[0116] Example 1

[0117] (1) Providing a degradable prostate stent body 100 and performing electrochemical polishing treatment on its surface:

[0118] This embodiment uses a magnesium prostate stent. The magnesium prostate stent body is ultrasonically cleaned in deionized water and anhydrous ethanol for 10 minutes in sequence, and then taken out and completely dried in a vacuum oven at 45°C.

[0119] The dried magnesium prostate stent was placed in a 1.2 mol / L phosphate electrolyte with a current density of 4A / cm2 and a stainless steel plate as the cathode for electrochemical polishing for 20 minutes. Finally, it was ultrasonically cleaned with deionized water for 10 minutes and completely dried in a vacuum oven at 45°C.

[0120] (2) forming a passivation layer 110 on the surface of the degradable prostate stent body 100, wherein the passivation layer 110 is a magnesium fluoride layer:

[0121] The magnesium prostate stent body obtained in step (1) was immersed in a 0.7 mol / L sodium fluoride solution for 40 minutes, then the magnesium prostate stent body was taken out, ultrasonically cleaned with deionized water for 10 minutes, and then completely dried in a 45° C. vacuum oven.

[0122] (3) forming an intermediate layer 120 on the surface of the degradable prostate stent body 100:

[0123] (3.1) Preparation of intermediate layer 120 slurry:

[0124] 1 g of dopamine hydrochloride powder was weighed and dissolved in 100 mL of Tris-HCl buffer, the pH value of which was 8.5, and stirred with a magnetic stirrer until completely dissolved to obtain a dopamine solution. The dopamine solution was placed at room temperature for self-polymerization reaction for 24 hours to obtain a polydopamine dispersion.

[0125] (3.2) Impregnation:

[0126] The magnesium prostate stent body obtained in step (2.3) is immersed in the polydopamine dispersion obtained in step (3.1) and allowed to stand in the dark for 3 hours. Then, the magnesium prostate stent body is taken out from the polydopamine dispersion, thoroughly washed with deionized water for 5 minutes, and finally completely dried in a vacuum oven at 45°C.

[0127] (4) Preparation of anti-tumor degradable prostate stent:

[0128] (4.1) Preparation of anti-tumor drug slurry:

[0129] (4.1.1) Providing a suspension of a prostate cancer cell membrane-MOF composite material:

[0130] 1 g of ZIF-8 was weighed and dissolved in 100 mL of deionized water. Subsequently, 0.5 g of ginsenoside, 0.5 g of abiraterone, and 0.5 g of licorice chalcone were dissolved in the ZIF-8 solution. The mixture was stirred and reacted at room temperature for 4-8 h to obtain solution A.

[0131] Prostate cancer cells were cultured with culture medium to 70% of the surface area of ​​the culture dish, and then 2 mL of EDTA-free trypsin solution was used to digest the prostate cancer cells and collect the prostate cancer cell suspension. Subsequently, 2 mL of cell lysis buffer was used to lyse the prostate cancer cell membrane and the obtained prostate cancer cell membrane was dissolved in PBS buffer to prepare a prostate cancer cell membrane suspension. The concentration of the prostate cancer cell membrane suspension was about 5 mg / mL.

[0132] Solution A and the prostate cancer cell membrane suspension are extruded at both ends of a membrane extruder to obtain a suspension of a MOF composite material wrapped by the prostate cancer cell membrane.

[0133] (4.1.2) Providing a suspension of an anti-tumor drug active ingredient-hyaluronic acid-prostate cancer cell membrane-MOF composite material:

[0134] 2 g of hyaluronic acid was weighed and dissolved in 100 mL of deionized water to form a hyaluronic acid solution. 0.3 g of 3-mercaptopropionic acid (3-MPA) was added as a thiol-reducing agent, 0.86 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 0.52 g of N-hydroxysuccinimide (NHS) were added as catalysts, and the reaction was carried out at room temperature for 4 h. After the reaction was completed, unreacted 3-mercaptopropionic acid and by-products were removed by dialysis to obtain a thiol-modified hyaluronic acid solution.

[0135] A suspension of the prostate cancer cell membrane-ZIF-8 composite material was added to the hyaluronic acid solution to obtain a solution B, and the solution B was stirred on a magnetic stirrer at 500 rpm for 1 hour to form an anti-tumor drug slurry.

[0136] (4.2) forming a sustained-release layer 130 on the surface of the degradable prostate stent:

[0137] The magnesium prostate stent obtained in step (3.2) is immersed in the anti-tumor drug slurry obtained in step (4.1), and the anti-tumor drug slurry impregnated with the magnesium prostate stent is placed on a shaker at a speed of 60 rpm, shaken for 20 hours, taken out, naturally evaporated at room temperature, and then fully washed with deionized water for 5 minutes, and finally completely dried in a 90°C vacuum oven to obtain an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent.

[0138] Example 2

[0139] The process is the same as in Example 1 above, except that after (1), (2) forming the passivation layer 110 on the surface of the degradable prostate stent body 100 is not performed, thereby obtaining an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent.

[0140] Example 3

[0141] Except for the following differences, it is the same as Example 1:

[0142] (2) forming a passivation layer 110 on the surface of the degradable prostate stent body 100, wherein the passivation layer 110 is a hydroxide layer:

[0143] The magnesium prostate stent body obtained in step (1) is placed in a high-pressure reactor, and a 1M NaOH solution is added to carry out a hydrothermal reaction for 28 hours at a reaction temperature of 40 to 100°C. The magnesium prostate stent body is then taken out and ultrasonically cleaned with deionized water for 5 minutes. The cleaning is repeated three times, and the stent body is taken out and completely dried in a vacuum oven at 45°C.

[0144] Example 4

[0145] Except for the following differences, it is the same as Example 1:

[0146] (2) forming a passivation layer 110 on the surface of the degradable prostate stent body 100, wherein the passivation layer 110 is a polydioxanone layer:

[0147] The magnesium prostate stent body obtained in step (1) was immersed in a 1wt% polydioxanone solution and allowed to stand for 4 hours. The magnesium prostate stent body was then taken out and placed in a 45°C vacuum oven to completely dry, cooled to room temperature, and finally washed with deionized water and anhydrous ethanol for 5 minutes in turn, and dried at room temperature after washing.

[0148] Example 5

[0149] Except for the following differences, it is the same as Example 1:

[0150] (4.1.2) Providing a suspension of an anti-tumor drug active ingredient-hyaluronic acid-prostate cancer cell membrane-MOF composite material:

[0151] 2 g of hyaluronic acid was weighed and dissolved in 100 mL of deionized water to form a hyaluronic acid solution. 0.3 g of epichlorohydrin was added as a hydroxylation agent and reacted at room temperature for 4 h. After the reaction was completed, unreacted epichlorohydrin and by-products were removed by dialysis to obtain a hydroxyl-modified hyaluronic acid solution.

[0152] A suspension of the prostate cancer cell membrane-ZIF-8 composite material was added to the hyaluronic acid solution to obtain a solution B, and the solution B was stirred on a magnetic stirrer at 500 rpm for 1 hour to form an anti-tumor drug slurry.

[0153] Example 6

[0154] Except for the following differences, it is the same as Example 1:

[0155] (4.1.1) Providing a suspension of a prostate cancer cell membrane-COF composite material:

[0156] 1 g of TPPA-COF was weighed and dissolved in 100 mL of deionized water. Subsequently, 0.5 g of ginsenoside, 0.5 g of abiraterone, and 0.5 g of licorice chalcone were dissolved in the ZIF-8 solution. The mixture was stirred at room temperature for 4-8 h to obtain solution A.

[0157] Prostate cancer cells were cultured with culture medium to 70% of the surface area of ​​the culture dish, and then 2 mL of EDTA-free trypsin solution was used to digest the prostate cancer cells and collect the prostate cancer cell suspension. Subsequently, 2 mL of cell lysis buffer was used to lyse the prostate cancer cell membrane and the obtained prostate cancer cell membrane was dissolved in PBS buffer to prepare a prostate cancer cell membrane suspension. The concentration of the prostate cancer cell membrane suspension was about 5 mg / mL.

[0158] Solution A and the prostate cancer cell membrane suspension are extruded at both ends of a membrane extruder to obtain a suspension of a COF composite material wrapped by the prostate cancer cell membrane.

[0159] Example 7

[0160] The process is the same as in Example 1 above, except that (3) forming the intermediate layer 120 on the surface of the degradable prostate stent body 100 is not performed after (2), thereby obtaining an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent.

[0161] Comparative Example 1

[0162] Except that (4.1.2) is not performed after (4.1.1), that is, no linker is used, the rest is the same as the above Example 1 to obtain an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent.

[0163] Degradability test experiment

[0164] The anti-tumor degradable prostate stents containing Chinese medicine sustained-release agents prepared in Examples 1 to 7 were immersed in artificial urine, and the artificial urine was changed every other week. Starting from 60 days, short flocculent degradation products were observed to begin to appear on the surface of the anti-tumor degradable stents containing Chinese medicine sustained-release agents prepared in Examples 1 to 7. Between 60 days and 90 days, the number of short flocculent degradation products increased, and on the 90th day, the anti-tumor degradable prostate stent containing Chinese medicine sustained-release agents was completely decomposed into crumbs.

[0165] Biocompatibility performance test experiment

[0166] The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent prepared by the methods of Examples 1 to 7 of the present invention was prepared by wire cutting to prepare a Φ12×2 mm block sample, which was sterilized by ultraviolet irradiation for 4 h and then the surface area / extract volume ratio was 1.25 cm 2 / mL standard extract preparation, the specific operation is as follows: the sterilized sample is immersed in serum-free DMEM culture medium, and the extraction is carried out in a cell culture incubator at 37°C and 5% CO2. The extraction time is 24h, and the extraction stock solution of the samples of Examples 1-7 is obtained, sealed, and stored in a refrigerator at 4°C for later use.

[0167] After MC3T3-E1 cells were revived and passaged, they were suspended in DMEM cell culture medium and seeded on 96-well plates to a final cell concentration of 2-5×10 4 / mL. The negative control group was DMEM cell culture medium, and 10% dimethyl sulfoxide (DMSO) was added to the culture medium as a positive control. The experimental group was added with 100% extract and cultured in a 37°C, 5% CO2 incubator. After 1 or 3 days, the culture plates were taken out and the cell viability test was performed using the CCK8 kit.

[0168] In Example 1, the cell survival rate was 132% after one day of culture, and the cell survival rate was 124% after three days of culture.

[0169] In Example 2, the cell survival rate was 108% after one day of culture, and the cell survival rate was 100% after three days of culture.

[0170] In Example 3, the cell survival rate was 118% after one day of culture, and the cell survival rate was 111% after three days of culture.

[0171] In Example 4, the cell survival rate was 119% after one day of culture, and the cell survival rate was 112% after three days of culture.

[0172] In Example 5, the cell survival rate was 120% after one day of culture, and the cell survival rate was 114% after three days of culture.

[0173] In Example 6, the cell survival rate was 128% after one day of culture, and the cell survival rate was 118% after three days of culture.

[0174] In Example 7, the cell survival rate was 119% after one day of culture, and the cell survival rate was 111% after three days of culture.

[0175] like Figure 4 As shown, during the entire culture period, the cell activity of all experimental materials was 100% or above, indicating that the extracts of all materials did not cause toxicity to MC3T3-E1 cells.

[0176] Corrosion performance test experiment

[0177] Electron microscopy:

[0178] The anti-tumor degradable prostate stents containing Chinese medicine sustained-release agents prepared in Example 1, Example 7 and Comparative Example 1 were immersed in simulated urine at 37° C. and samples were taken regularly. The morphological changes of the surface of the anti-tumor degradable prostate stents were observed using a scanning electron microscope (SEM).

[0179] like Figure 5 As shown, Example 1 uses thiol-modified hyaluronic acid as a connector, and has an anti-tumor degradable prostate stent with a passivation layer 110 and a polydopamine intermediate layer 120. On the second day, under a 200μm electron microscope scan, the surface is relatively smooth; on the 14th day, under a 50μm electron microscope scan, the surface is slightly uneven, with slight cracks and defects.

[0180] like Figure 6As shown, Example 7 uses thiol-modified hyaluronic acid as a connector, and the anti-tumor degradable prostate stent without a polydopamine intermediate layer 120 has an uneven surface with multiple cracks and defects under a 50 μm electron microscope scan on the 14th day; and an even more obvious surface unevenness with multiple cracks and defects under a 20 μm electron microscope scan on the 14th day.

[0181] like Figure 7 As shown, the anti-tumor degradable prostate stent without a linker used in Comparative Example 1 had a large number of corrosion pits on the surface under a 50 μm electron microscope scan on the 14th day, and the degree of corrosion was severe; under a 20 μm electron microscope scan on the 14th day, there were a large number of corrosion pits on the surface, and the degree of corrosion was more severe and more obvious.

[0182] Specific recognition performance test

[0183] like Figure 8 As shown, it can be seen that under microscopic tissue scanning at 200nm, when the drug molecules (such as ginsenosides, etc.) carried on the prostate cancer cell membrane come into contact with tumor cells, the receptors on the prostate cancer cell membrane can bind to the corresponding ligands on the surface of the tumor cells to achieve drug targeted therapy.

[0184] Anti-tumor effect performance test

[0185] Prostate cancer cells (PC3) were inoculated in a cell culture medium, and an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent prepared according to the method of Example 1 of the present invention was prepared by wire cutting to prepare a Φ12×2 mm block sample, which was sterilized by ultraviolet irradiation for 4 hours and then immersed in a cell culture medium. Samples were taken regularly to determine the survival rate of the prostate cancer cells.

[0186] After 1 day of culture, the cell activity against prostate cancer cells was 90.32%;

[0187] After 3 days of culture, the cell activity against prostate cancer cells was 68.89%;

[0188] like Fig. 9 As shown, the extract of the anti-tumor degradable prostate stent prepared in Example 1 of the present invention has a significant inhibitory effect on prostate cancer cells, and the inhibitory effect on prostate cancer cells gradually increases over time.

[0189] Based on the above-mentioned embodiments of the present invention, in the absence of explicit negation or conflict, the technical features of one embodiment may be beneficially combined with one or more other embodiments.

[0190] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent, characterized in that: include: Degradable prostate stent body; A sustained-release layer, wherein the sustained-release layer is formed on the surface of the degradable prostate stent body, and the sustained-release layer contains a carrier, a linker, and an active ingredient of an anti-tumor drug carried by the carrier, Wherein, the carrier is a nanoporous material, the nanoporous material includes a prostate cancer cell membrane, and the linker is one or more of hyaluronic acid, polytrimethylene carbonate, polyvinyl alcohol, gelatin, chitosan, cellulose, polyacrylamide, poly-N-isopropylacrylamide, polyvinyl pyrrolidone, and poly(hydroxyethyl methacrylate) modified with hydroxyl or thiol groups; The active ingredients of the anti-tumor drug contain traditional Chinese medicine monomers, and the traditional Chinese medicine monomers are one or more of licorice chalcone, ginsenoside, curcumin, ganoderma lucidum polysaccharide, tanshinone IIA, and dendrobium.

2. The anti-tumor degradable prostate stent according to claim 1, characterized in that: The active ingredients of the anti-tumor drug also contain western medicine monomers, which include one or more of enzalutamide, abiraterone, megestrol acetate, flutamide and its derivatives, bicalutamide, carboplatin, cisplatin, and etoposide.

3. The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to claim 1, characterized in that: The nanoporous material also includes one or more of plant vesicles, bacterial vesicles, metal-polyphenol copolymers, micelles formed by cationic surfactants, metal-organic frameworks, and covalent-organic frameworks.

4. The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to claim 1, characterized in that: The surface of the degradable prostate stent body is subjected to electrochemical polishing treatment, and the degradable prostate stent further comprises: A passivation layer is arranged on the surface of the degradable prostate stent body after electrochemical polishing, wherein the sustained-release layer is arranged on the surface of the passivation layer away from the degradable prostate stent body.

5. The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to claim 4, characterized in that: The passivation layer is one or more of a magnesium fluoride layer, a polydioxanone layer, or an alkalized hydroxide layer.

6. The anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent according to claim 4, characterized in that: Also includes: The intermediate layer is arranged between the passivation layer and the sustained-release layer. The intermediate layer is a polydopamine material layer. The thickness of the polydopamine material layer is 1 to 5 μm.

7. A method for preparing an anti-tumor degradable prostate stent containing a Chinese medicine sustained-release agent, characterized in that: The following steps are involved: Step S1, providing a degradable prostate stent body; Step S2, providing an anti-tumor drug slurry, wherein the anti-tumor drug slurry contains a carrier, a linker, and an anti-tumor drug active ingredient, wherein the anti-tumor drug active ingredient is connected to the surface of the carrier by the linker, Wherein, the carrier is a nanoporous material, the nanoporous material includes a prostate cancer cell membrane, and the linker is one or more of hyaluronic acid, polytrimethylene carbonate, polyvinyl alcohol, gelatin, chitosan, cellulose, polyacrylamide, poly-N-isopropylacrylamide, polyvinyl pyrrolidone, and poly(hydroxyethyl methacrylate) modified with hydroxyl or thiol groups; The active ingredients of the anti-tumor drug contain Chinese medicine monomers, and the Chinese medicine monomers are one or more of licorice chalcone, ginsenoside, curcumin, ganoderma lucidum polysaccharide, tanshinone IIA, and dendrobium; Step S3, immersing the degradable prostate stent body in the anti-tumor drug slurry to form a sustained-release layer on the surface of the degradable prostate stent body, thereby obtaining an anti-tumor degradable prostate stent containing a traditional Chinese medicine sustained-release agent.

8. The preparation method according to claim 7, characterized in that: In the step S3, before the degradable prostate stent body is immersed in the anti-tumor drug slurry, the degradable prostate stent body is pretreated, wherein the pretreatment includes: Performing electrochemical polishing on the surface of the degradable prostate stent body; The surface of the degradable prostate stent body is passivated to form a passivation layer on the surface of the degradable prostate stent body.

9. The preparation method according to claim 8, characterized in that: The passivation treatment comprises: The degradable prostate stent body is immersed in hydrofluoric acid or sodium fluoride solution to form the magnesium fluoride layer on the surface of the degradable prostate stent body. Alternatively, a polydioxanone layer or an alkalized hydroxide layer is coated on the surface of the degradable prostate stent body.

10. The preparation method according to claim 8, characterized in that: The pre-processing further comprises: providing a polydopamine dispersion; The degradable prostate stent body is immersed in the polydopamine dispersion to form a polydopamine material layer on the passivation layer on the surface of the degradable prostate stent body.

Images