Drug-carrying medical device, drug coating, preparation method and application thereof

Abstract

This invention discloses a drug-loaded medical device, a drug coating, its preparation method, and its application. The drug coating comprises the following components: 0.1 wt%–29.9 wt% drug, 70 wt%–99 wt% carrier substance, and 0.01 wt%–5 wt% surfactant. The carrier substance comprises at least one of gelatin, sodium polyacrylate, polyacrylic acid, polyvinyl alcohol, sodium alginate, povidone, dextran, polycaprolactone, chitosan, polylactic acid, glycolide-lactide copolymer, polyglycolic acid, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, stearic acid, mixed fatty acid glycerides, polyhydroxyl stearate, hydrogenated palm oil glycerides, carbomer, poloxamer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose, and polyvinylpyrrolidone. The molecular weight of the carrier substance is 4000–600000. The drug coating of the present invention has excellent effects in terms of adhesion, peeling, coefficient of friction, stability, and drug release.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a drug-carrying medical device, a drug coating, and a preparation method and application thereof. Background Art

[0002] Usually, for the purpose of sampling and ablation, it is necessary to use medical devices that puncture the subject's body tissue, such as biopsy needles, ablation needles, etc.

[0003] A biopsy needle is a medical device used for obtaining samples of tumors (including pyramidal tumors and unknown tumors) or cancer tissues and aspirating cells from various organs such as the kidney, liver, lung, breast, thyroid, prostate, pancreas, testicle, uterus, ovary, and body surface. At present, biopsy needle products are basically composed of a sheath, a needle holder, an inner needle holder, a needle tube, and an inner needle rod. When in use, the needle needs to penetrate the skin to a certain depth to reach the site to be biopsied, and then obtain samples for subsequent testing. However, in the current process of using a biopsy needle for puncture and sampling, it is easy to puncture tumors or cancer cells, causing the spread of tumors or cancer cells, and increasing the risk of tumor or cancer spread during the biopsy process.

[0004] Ablation needle is a commonly used medical device in ablation. Ablation is mostly performed under ultrasound guidance and local anesthesia. Special ablation equipment is used to send the ablation needle into the diseased tissue, and high temperature, low temperature and other methods are used to cause necrosis of the diseased tissue, thereby achieving the purpose of treatment. The ablation needle generally includes a needle tip, a needle rod, a handle, a slider, a hose, a needle connector, etc. Tumor or cancer ablation needles are mainly used for ablation treatment of liver tumors, breast tumors, kidney tumors in general surgery, lung tumors in thoracic surgery, gynecological uterine fibroids, and soft tissue tumors or cancers in other parts. Summary of the invention

[0005] In view of the deficiencies of the prior art, the present invention adds a drug coating on the basis of the existing medical devices for puncturing the body tissue of the subject, that is, at least one layer of drug coating is coated on the surface of the medical device to be loaded with drugs, and the drug coating falls off during the puncture process, and the drug stays and is released in the puncture track in the body.

[0006] In order to solve the problems existing in the prior art, the technical solution of the present invention is as follows:

[0007] In a first aspect, the present invention provides a drug coating, which comprises the following components, based on the total weight of the raw materials: 0.1 wt%-29.9 wt% of the drug, 70 wt%-99 wt% of the carrier material, and 0.01 wt%-5 wt% of the surfactant;

[0008] The drug includes at least one of an anticancer drug, an antibacterial and anti-inflammatory drug, a hemostatic drug, an analgesic drug, and a wound healing drug;

[0009] The carrier material comprises at least one of gelatin, sodium polyacrylate, polyacrylic acid, polyvinyl alcohol, sodium alginate, povidone, dextran, polycaprolactone, chitosan, polylactic acid, glycolide-lactide copolymer, polyglycolide, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, stearic acid, mixed fatty acid glyceride, polyoxyl stearate, hydrogenated palm oil glyceride, carbomer, poloxamer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose and polyvinyl pyrrolidone; the molecular weight of the carrier material is 4000-600000;

[0010] The surfactant includes at least one of stearic acid, fatty acid glyceride, sodium dodecylbenzene sulfonate, quaternary ammonium compound, fatty acid sorbitan, polysorbate, azone, lecithin, amino acid type and betaine type.

[0011] Preferably, based on the total mass of the raw materials, it also includes 2wt% or less of a humectant;

[0012] The moisturizing agent includes at least one of glycerin, propylene glycol, butylene glycol, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, and sorbitol.

[0013] Preferably, based on the total weight of the raw materials, the following components are included: 1 wt%-19.9 wt% of the drug, 80 wt%-98 wt% of the carrier substance and 0.01 wt%-1 wt% of the surfactant.

[0014] In a second aspect, the present invention provides a method for preparing the above-mentioned drug coating, comprising the following steps:

[0015] Step 1: Add the raw materials into a suitable amount of solvent, control the temperature below 40°C to dissolve, mix evenly, and obtain a coating solution;

[0016] Step 2: applying the coating solution to the surface of the medical device to be loaded with drugs, and drying to obtain a drug coating;

[0017] In the step 1, the temperature during the mixing process is 35-65°C;

[0018] In the step 2, the temperature during the coating process is 25-50° C.; the temperature during the drying process is 40-50° C., and the ambient humidity during the drying process is below 10% RH;

[0019] The prepared drug coating has a solvent content of 2 wt%-5 wt%;

[0020] The friction coefficient of the prepared drug coating is below 0.6.

[0021] Preferably, the solvent comprises water and / or ethanol;

[0022] Preferably, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by spraying: controlling the temperature of the coating solution to 28-45°C, stirring the coating solution at the same time, and controlling the coating time within 6 hours; the spraying parameters include: spraying speed of 0.2-0.7 ml / min, air inlet temperature of 40-50°C, air inlet speed of 1.5-2.0 m 3 / min.

[0023] Preferably, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: including controlling the temperature of the coating solution to 28°C-35°C and the coating time to be within 12 hours; immersing the part of the medical device to be loaded with drugs to be coated in the coating solution, taking out the medical device to be loaded with drugs from the coating solution, accelerating the speed to 0.1-4 cm / s, and horizontally rotating the medical device to be loaded with drugs at a speed of 10-20r / min, so that the coating solution is evenly dispersed on the surface of the medical device to be loaded with drugs as the temperature decreases and the solvent evaporates, thereby obtaining a drug coating.

[0024] Preferably, the friction coefficient of the drug coating is 0.4-0.6.

[0025] Preferably, the viscosity of the coating solution prepared in step 1 is 500-5000 mPa·s at 30°C.

[0026] In a third aspect, the present invention provides a use of the drug coating described above or the drug coating prepared by the method described above in preparing a drug-loaded medical device for biopsy or tumor ablation.

[0027] In a fourth aspect, the present invention provides a drug-carrying medical device, wherein the drug coating described above or the drug coating prepared by the method described above is coated on the surface of the drug-carrying medical device.

[0028] The beneficial effects of the present invention include at least:

[0029] Since existing punctures have certain risks, including at least one of bleeding, pain, infection, etc., the present invention adds a drug-carrying coating on the basis of existing medical devices for puncturing the body tissue of the subject. During the puncture process, the drug can be carried into the puncture track (or called the needle track), which effectively compensates for the disadvantages of the puncture and reduces the degree of harm caused by the puncture.

[0030] The drug coating of the present invention has the characteristic of reducing puncture resistance, can alleviate the pain of the subject during use, and increase the applicability of medical devices (such as biopsy needles, ablation needles, etc.) for puncturing the subject's body tissue in clinical use.

[0031] The drug coating of the present invention has the characteristics of directional shedding and drug release, and will not fall off in vitro. After entering the body, the coating can effectively fall off and release the drug under the influence of the internal environment, and the coating can be degraded in the body.

[0032] The drug coating of the invention is firmly combined with the surface of the drug-carrying medical device, the drug is evenly dispersed, and is easy to fall off in the body.

[0033] The drug coating of the present invention is a solid dispersion, which can change the dispersion form of the drug in the coating. The drug is dissolved with the carrier material and then dried to form a coating. The drug is dispersed in the form of molecules and then forms a mixture with the carrier material.

[0034] The drug coating of the present invention also has the characteristic of controlled release of drugs in vivo. By controlling the difference of coating materials, the drug release rate in vivo is 0.2 mg / h-18 mg / h, which can improve the safety and effectiveness of clinical use.

[0035] The drug coating of the present invention can be well combined with the surface of the medical device to be loaded with drugs. Usually, the surface of the medical device to be loaded with drugs is made of stainless steel, nickel-titanium alloy, platinum-chromium alloy, polytetrafluoroethylene, polyethylene, polyester, etc. It has excellent firmness and will not fall off after multiple punctures in vitro. Moreover, when used clinically, more than 90% of the drug coating can be fallen off after one puncture in vivo.

[0036] The drug coating of the present invention can reduce the friction force of puncture, reduce the friction coefficient during use, and greatly improve the adaptability of clinical use.

[0037] When the drug-loaded medical device product of the present invention is placed for a long time after preparation, various indicators (such as coating firmness, in vivo removability, drug release, and friction coefficient) will not undergo significant changes that affect performance, and the product has good stability.

[0038] The drug-loaded medical device of the present invention can be widely used in situations where puncturing of a subject's body tissue is required, including but not limited to the sampling and ablation treatment of tumor or cancer cells / tissues.

[0039] The features and advantages of the present invention will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 The friction coefficient comparison results of the uncoated biopsy needle and the coated biopsy needle coated with the drug coating prepared in Example 1 are shown.

[0041] Figure 2 The relationship between the moisture content and the friction coefficient of the drug coating prepared in Example 1 is shown.

[0042] FIG3( a ) shows a drug-loaded biopsy needle coated with the drug coating prepared in Example 1, wherein the drug coating contains 0.1 wt % carmine.

[0043] FIG3( b ) shows the coating residue in the puncture track after the drug-loaded biopsy needle punctures the ex vivo tissue. DETAILED DESCRIPTION

[0044] In order to make the purpose, technical scheme and beneficial effects of the present invention clearer, the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments. Examples of the embodiments are shown in the accompanying drawings. It should be understood that the specific embodiments described in the following embodiments of the present invention are only exemplary descriptions of the specific embodiments of the present invention, and are intended to be used to explain the present invention, but do not constitute a limitation of the present invention.

[0045] The endpoints and any value of the scope disclosed in this article are not limited to this accurate scope or value, and these scopes or values ​​should be understood as comprising values ​​close to these scopes or values.For numerical range, between the endpoint values ​​of each scope, between the endpoint values ​​of each scope and a separate point value, and between separate point values, can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered as specifically disclosed in this article.In the description of the application, unless otherwise stated, the meaning of similar words such as "multiple / multiple" is two / kinds or more than two / kinds.In addition, the terms "include", "comprise" and any distortion thereof are intended to cover non-exclusive inclusions.

[0046] In a first aspect, the present invention provides a drug coating, which comprises the following components, based on the total weight of the raw materials: 0.1 wt%-29.9 wt% of the drug, 70 wt%-99 wt% of the carrier material, and 0.01 wt%-5 wt% of the surfactant;

[0047] In the present invention, the drug in the drug coating provides corresponding efficacy, and the selected drug should have a certain solubility. The drug can be dissolved in solvent water / or ethanol, and the solubility is not less than 0.5%.

[0048] In the present invention, the drug includes at least one of an anticancer drug, an antibacterial and anti-inflammatory drug, a hemostatic drug, an analgesic drug, and a wound healing promoting drug.

[0049] In some preferred embodiments of the present invention, the anticancer drug includes at least one of fluorouracil, paclitaxel, bleomycin, fluorouracil, epirubicin, gemcitabine hydrochloride, mitoxantrone hydrochloride, ifosfamide, elenin, and bortezomib.

[0050] In some preferred embodiments of the present invention, the antibacterial and anti-inflammatory drugs include at least one of tigecycline, minocycline, doxycycline, metacycline, demeclocycline, tetracycline, oxytetracycline, chloramphenicol, thiamphenicol, norfloxacin, ciprofloxacin, ofloxacin, levofloxacin hydrochloride, lomefloxacin, fleroxacin, sparfloxacin, ampicillin, amoxicillin, carbenicillin, piperacillin, cephalothin, cefazolin, ceftriaxone, cefapirin, cefuroxime, cefuroxime sodium.

[0051] In some preferred embodiments of the present invention, the hemostatic drug includes at least one of ethidiumsulfate, thrombin (batroxobin / reptilase), desmopressin, vitamin K1, vitamin K3, vitamin K4, fibrinogen, tranexamic acid, aminoacetic acid, aminobenzoic acid, aprotinin, carbaclorol, and carbazochrome sulfonate.

[0052] In some preferred embodiments of the present invention, the analgesic drug comprises at least one of acetaminophen, ibuprofen, codeine, tramadol, morphine, fentanyl, hydromorphone, gabapentin, and pregabalin.

[0053] In some preferred embodiments of the present invention, the wound healing promoting drug comprises at least one of epidermal growth factor, chitosan and Yunnan Baiyao powder.

[0054] In the present invention, the carrier material is a high molecular polymer, has biodegradable properties, is harmless to the human body, has a molecular weight of 4000-600000, and has a viscosity of 20-2000 mPa·s at 0.5% concentration and 30°C. The carrier material is solid at room temperature, but can fall off under the action of body temperature when encountering grease or body fluids. It has the performance of realizing in vitro drug loading and being able to firmly combine with the surface of drug-loaded medical devices, and being able to quickly fall off from drug-loaded medical devices in vivo, so that the drug coating can be delivered to the target location without the need for other exogenous sources and without affecting puncture. As the main matrix of the drug coating, the carrier material should have multiple properties, including good solubility, reliable bonding strength between the drug coating and the surface of the drug-loaded medical device (i.e., the surface of the drug-loaded medical device that contacts the punctured body tissue) after the drug coating is formed, so that the drug coating can be firmly bonded to the surface of the drug-loaded medical device and can control the release of the drug with a high release rate. The membrane surface should have good smoothness and should be able to fall off quickly in the body after puncture. The drug delivery rate should be high and the loss rate should be low during the delivery process.

[0055] In the present invention, the carrier material is of medical grade or pharmaceutical grade.

[0056] In the present invention, the carrier material includes at least one of gelatin sodium polyacrylate, polyacrylic acid, polyvinyl alcohol, sodium alginate, povidone, dextran, polycaprolactone, chitosan, polylactic acid, glycolide-lactide copolymer, polyglycolide, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, stearic acid, mixed fatty acid glyceride, stearic acid polyoxyl esters, hydrogenated palm oil glyceride, carbomer, poloxamer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose, and polyvinyl pyrrolidone;

[0057] In the present invention, the drug coating contains an active agent, which has a lubricating effect and can improve the smoothness of the coating surface. Compared with ordinary medical devices, it can reduce the resistance during the puncture process and improve clinical applicability.

[0058] In the present invention, the surfactant includes at least one of stearic acid, fatty acid glyceride, sodium dodecylbenzene sulfonate, quaternary ammonium compound, fatty acid sorbitan, polysorbate, azone, lecithin, amino acid type, and betaine type.

[0059] In some preferred embodiments, the drug coating comprises the following components, based on the total weight of the raw materials: 1 wt%-19.9 wt% of the drug, 80 wt%-98 wt% of the carrier material, and 0.1 wt%-1 wt% of the surfactant.

[0060] In some preferred embodiments, the drug coating further comprises a humectant in an amount of less than 2 wt% based on the total weight of the raw materials. The humectant has a certain moisturizing effect. Adding the humectant can better control the moisture content of the drug coating, improve the stability of the product, better avoid problems such as cracking of the coating due to low moisture content and drying during placement / storage, and better ensure that the moisture content of the coating is within the range of 2 wt%-5 wt%.

[0061] In some more preferred embodiments, the moisturizer includes at least one of glycerin, propylene glycol, butylene glycol, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, and sorbitol.

[0062] In some preferred embodiments, the drug coating further comprises less than 0.1 wt % of a color enhancer based on the total weight of the raw materials.

[0063] In some more preferred embodiments, the color enhancer includes at least one of carmine, sunset red, and monascus red.

[0064] In some more preferred embodiments of the present invention, the carrier material includes gelatin. Gelatin is a peptide molecule polymer material and a multi-stage hydrolysis product of collagen. The gelatin used in the present invention is derived from pig skin and is prepared by an acid method.

[0065] In some further more preferred embodiments of the present invention, the molecular weight of gelatin is 30000-300000, and when the concentration is 6.67%, the viscosity of gelatin is 2-5 mPa·s at 60°C; when the concentration is 0.5%, the viscosity is 50-500 mPa·s at 30°C.

[0066] In some further more preferred embodiments of the present invention, the carrier material includes polyvinyl alcohol, has an average molecular weight of 16,000-20,000, a viscosity of 20.0-30.0 mPa·s, and is water-soluble.

[0067] In some further more preferred embodiments of the present invention, the carrier material includes polyethylene glycol 4000, with an average molecular weight of about 4000. When the concentration is 0.5%, the viscosity is 50-250 mPa·s at 30°C. It has excellent lubricity, moisturizing, dispersibility, adhesiveness, antistatic agent and softener, and has good water solubility.

[0068] In some further more preferred embodiments of the present invention, the carrier material includes polyacrylic acid with a molecular weight of 500-5000. When the concentration in the solution is 15%-25%, the viscosity is 10000-20000 mPa·s; when the concentration is 0.5%, at 30°C, the viscosity is 1500-2000 mPa·s; it can be fully dissolved in an aqueous solution, has good viscosity, and improves the firmness of the coating.

[0069] In some more preferred embodiments of the present invention, the surfactant is Tween (or polysorbate), a non-ionic surfactant.

[0070] In some further more preferred embodiments of the present invention, the surfactant is Tween (or polysorbate), and the polysorbate is Tween 60 and / or Tween 80, with an average molecular weight of 200-600 and a viscosity of 200-800 mPa·s.

[0071] In the present invention, the raw materials are the components of the drug coating other than the solvent, including the drug, carrier material and surfactant, and optionally humectant, color enhancer and the like.

[0072] In a second aspect, the present invention provides a method for preparing the above-mentioned drug coating, comprising the following steps:

[0073] 1. Add the raw materials into a proper amount of solvent, control the temperature below 40°C to dissolve, mix evenly, and obtain a coating solution;

[0074] 2. applying the coating solution to the surface of the medical device to be loaded with drugs, and drying to obtain a drug coating;

[0075] In the step 1, the temperature during the mixing process is 35-65°C;

[0076] In the step 2, the temperature during the coating process is 25-50° C.; the temperature during the drying process is 40-50° C., and the ambient humidity during the drying process is below 10% RH;

[0077] The prepared drug coating has a solvent content of 2 wt%-5 wt%;

[0078] The friction coefficient of the prepared drug coating is below 0.6.

[0079] In step 1, there is no particular limitation on the order in which the drug and the carrier substance are dispersed in the solvent.

[0080] In the present invention, it is necessary to ensure that the coating solution is in a uniform solution state, which is one of the important conditions for ensuring that the properties of the coating surface meet the requirements.

[0081] In some preferred embodiments, in step 1, the mixture is uniformly mixed by stirring, and the stirring speed during the uniform mixing is set to 75 r / min to 150 r / min;

[0082] In some preferred embodiments, in step 1, the mixing is performed in a water bath at a temperature of 55-65°C.

[0083] In some preferred embodiments, the solvent includes water and / or ethanol.

[0084] In some more preferred embodiments, the solvent includes anhydrous ethanol with an ethanol concentration of 99.5%. When anhydrous ethanol is used, it can also be called a solubilizer.

[0085] In some preferred embodiments, the amount of the solvent is 65wt%-90wt%, based on the total mass of the raw materials and the solvent, so as to achieve a more suitable concentration and viscosity of the coating solution, and the formed drug coating has a higher density, better dispersibility, film-forming property, firmness, removability, drug release performance, friction coefficient, stability, etc.

[0086] In some preferred embodiments, step one includes adding a carrier substance gelatin into a container, adding a solvent, using a water bath magnetic stirrer, setting the stirring speed to 75-150 r / min, causing a slight vortex in the solution, stirring it in a water bath at 60-65° C., the solvent dissolves the carrier substance gelatin, and cooling the solution to below 40° C.; adding Tween 80 to the above solution and stirring evenly; adding a drug gemcitabine hydrochloride, stirring to dissolve it, mixing evenly, obtaining a clear and transparent coating solution, cooling it to 28-32° C., and the viscosity of the coating solution is 3000-4000 mPa·s.

[0087] In some preferred embodiments, step 1 includes adding a carrier substance gelatin into a container, adding a solvent, using a water bath magnetic stirrer, setting the stirring speed to 75-150 r / min, making the solution slightly vortexed, stirring it in a water bath at 60-65° C. to dissolve the carrier substance gelatin, and cooling the solution to below 40° C.; adding Tween 80 to the above solution and stirring evenly; taking a drug paclitaxel, adding anhydrous ethanol, stirring to dissolve it; mixing the above two solutions, controlling the temperature at 40° C.-45° C. in a closed container, fully stirring, mixing evenly, obtaining a clear and transparent coating solution, cooling it to 28° C.-32° C., and the viscosity of the coating solution is 2500-3500 mPa·s.

[0088] In some preferred embodiments, step one includes dispersing the carrier substance polyvinyl alcohol in a solvent to completely dissolve the polyvinyl alcohol; taking the carrier substance gelatin, adding it to the above polyvinyl alcohol solution, using a water bath magnetic stirrer, setting the stirring speed to 75-150r / min, so that the solution has a slight vortex, stirring it in a water bath at 60-65°C to dissolve the gelatin, and cooling the solution to below 40°C; adding Tween 80 to the above solution, and then adding glycerol, controlling the stirring speed so that bubbles are not generated, and stirring thoroughly and evenly; taking the drug fluorouracil, slowly adding it to the above solution, stirring to dissolve it, mixing evenly, obtaining a clear and transparent coating solution, cooling it to 28-32°C, and the viscosity of the coating solution is 3500-5000mPa·s.

[0089] In some preferred embodiments, step 1 includes dispersing the carrier substance polyacrylic acid in a solvent and stirring to dissolve it; taking the drug levofloxacin hydrochloride, slowly adding it to the above solution, stirring to dissolve it; taking the carrier substance gelatin, adding it to the above solution, using a water bath magnetic stirrer, setting the stirring speed to 75-150r / min, so that the solution has a slight vortex, stirring it in a water bath at 60-65°C to dissolve the gelatin, and cooling the solution to below 40°C; adding Tween 60 to the above solution, controlling the stirring speed so that bubbles are not generated, and fully stirring and mixing to obtain a clear and transparent coating solution with a viscosity of 2500-4000mPa·s.

[0090] In some preferred embodiments, the drug coating comprises two layers, and step one comprises:

[0091] 1. Preparation of the inner coating: take the carrier substance gelatin, add it to the container, then add the solvent, use a water bath magnetic stirrer, set the stirring speed to 75-150r / min, make the solution have a slight vortex, stir it in a water bath at 60-65°C, dissolve the carrier substance gelatin, and cool the solution to below 40°C; add Tween 80 to the above solution, control the stirring speed, it is not suitable to generate bubbles, and stir it thoroughly; take the drug paclitaxel, add anhydrous ethanol, and stir to dissolve it; mix the above two solutions, stir, mix evenly, obtain a clear and transparent solution, and prepare the inner coating solution, when the temperature is 30°C, the viscosity is 3000-4000mPa·s;

[0092] 2. Preparation of the outer coating: Take the carrier material polyvinyl alcohol, add it to the container, then add the solvent, stir to disperse and fully dissolve the carrier material polyvinyl alcohol; take the carrier material polyethylene glycol 4000, add it to the polyvinyl alcohol solution, stir to dissolve the carrier material polyethylene glycol 4000; take the drug ethylphenol sulfonamide, add it to the above solution, stir to dissolve it; take glycerol, add it to the above solution, stir to mix it evenly, control the stirring speed to 75-150r / min, preferably without bubbles, stir fully, mix evenly, obtain a clear and transparent solution, and prepare the outer coating solution with a viscosity of 500-2000mPa·s.

[0093] In the present invention, the drug-loaded medical device punctures the body tissue of a subject or a soft tissue-like material for detection, wherein the body tissue includes healthy and / or abnormal soft tissue.

[0094] In the present invention, soft tissue is relative to bone-like hard tissue. In a broad sense, soft tissue includes all tissues except bone-like hard tissue, such as skin, nerves, blood vessels, muscles, subcutaneous fat, organs, muscles, fascia, etc.

[0095] In some embodiments, the drug-loaded medical device of the present invention can be widely used in situations where puncturing of a subject's body tissue is required, including but not limited to the sampling and ablation treatment of tumor or cancer cells / tissues.

[0096] In some embodiments, the present invention adds a drug coating on the basis of existing medical devices that puncture the subject's body tissue, that is, at least one layer of drug coating is coated on the surface of the medical device to be loaded with drugs, and the drug coating falls off during the puncture process. The drug stays and is released in the puncture track in the body. When a tumor or cancer is punctured, the drug can effectively kill and inhibit tumor or cancer cells, greatly reducing the risk of tumor or cancer spreading during the process of puncturing the subject's body tissue.

[0097] In some embodiments, the drug-loaded medical device is a puncture biopsy device, which is a medical device commonly used to puncture a subject's body tissue.

[0098] In some preferred embodiments, the drug-loaded medical device is a drug-loaded biopsy needle. The existing biopsy needle is mainly suitable for obtaining human tumor or cancer tissue from the liver, kidney, prostate, breast, spleen, lymph nodes, and soft tissue, and diagnosing whether the lesion is malignant based on the morphology of the lesion tissue cells under the microscope. There may be certain risks when the operation is improper, such as tumor or cancer cell spread, bleeding, pain, infection, etc. (1. Tumor or cancer cell spread: When puncturing to obtain materials from lesion tissue cells, it is necessary to puncture the cyst, which will cause tumor cells or cancer cells to be contaminated on the biopsy needle. During the needle withdrawal process, tumor cells or cancer cells will remain in the needle tract, causing tumor cells or cancer cells to spread. 2. Bleeding: Since puncture biopsy is an invasive examination method, there are risks such as bleeding at the puncture point. 3. Pain: Biopsy needles are generally thin, most of which are about 1 mm, and puncture biopsy is usually performed under local anesthesia or general anesthesia, and generally does not cause pain. However, due to different personal tolerance and puncture sites, the response to postoperative pain is also different. 4. Infection: Infection at the puncture site may occur during the puncture process). While retaining the functions of a traditional biopsy needle, the drug-loaded biopsy needle can kill tumor cells or cancer cells remaining on the needle track after puncturing tumor tissue or cancer cell tissue, thereby reducing the risk of tumor cells or cancer cells spreading.

[0099] In some preferred embodiments, the drug-loaded medical device is a drug-loaded ablation needle, and a drug coating is applied to the surface of the drug-loaded ablation needle. The drug-loaded ablation needle can kill residual cancer cells after ablation while retaining the function of a traditional ablation needle, thereby reducing the risk of tumor recurrence.

[0100] In the present invention, the coating step can be applied by dipping or spraying. Dipping means immersing the medical device to be loaded with drugs in the coating solution, lifting the medical device to be loaded with drugs after all the parts to be loaded with the coating solution, and forming a drug coating on the surface of the medical device to be loaded with drugs after drying; spraying means using a spray gun or a disc atomizer, with the help of pressure or centrifugal force, to disperse into uniform and fine droplets, and applying them to the surface of the medical device to be loaded with drugs. During the spraying process, the coating solution will dry immediately to form a film of the drug coating.

[0101] In some preferred embodiments, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: including controlling the temperature of the coating solution to 28°C-35°C and the coating time to be within 12 hours; immersing the part of the medical device to be loaded with drugs to be coated in the coating solution, taking out the medical device to be loaded with drugs from the coating solution, accelerating the speed to below 0.1-4cm / s, and horizontally rotating the medical device to be loaded with drugs at a speed of below 10-20r / min, so that the coating solution is evenly dispersed on the surface of the medical device to be loaded with drugs as the temperature decreases and the solvent evaporates, and the coating solution is dried to control the moisture content within the range of 2wt%-5wt% to obtain a drug coating.

[0102] In some more preferred embodiments, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: including controlling the temperature of the coating solution to 30°C-32°C and the coating time to be within 8 hours; immersing the coating part of the medical device to be loaded with drugs in the coating solution, taking out the medical device to be loaded with drugs from the coating solution, increasing the speed by 0.1-1.5 cm / s, and horizontally rotating the medical device to be loaded with drugs at a speed of 15-20r / min, so that the coating solution decreases with the temperature and the solvent evaporates, and the coating solution is evenly dispersed on the surface of the medical device to be loaded with drugs, and after 50% of the water evaporates, an intermediate product of the medical device to be loaded with drugs is obtained; placing the intermediate product of the biopsy needle loaded with drugs at 40-50°C, drying for 10-30min, controlling the water content within the range of 2wt%-5wt%, and obtaining a medical device to be loaded with drugs with the drug coating evenly dispersed on the surface.

[0103] In some more preferred embodiments, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: controlling the temperature of the coating solution to 30°C-35°C, keeping it warm in a water bath, controlling the coating time to be within 8 hours, immersing the coating part of the medical device to be loaded with drugs in the coating solution, accelerating the speed to below 0.5 cm / s, and rotating the biopsy needle horizontally at a speed below 10 r / min, so that the coating solution decreases with the temperature and the water evaporates, and the coating solution is evenly dispersed on the surface of the biopsy needle, and after the water evaporates by 60%, an intermediate product of the drug-loaded medical device is obtained; placing the intermediate product of the drug-loaded medical device at 40-45°C, drying it for 10-30 minutes, controlling the water content to be within the range of 2wt%-5wt%, and obtaining a drug-loaded medical device with the drug coating evenly dispersed on the surface.

[0104] In some more preferred embodiments, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: including lowering the temperature of the coating solution to 28°C-30°C, and controlling the coating time within 12 hours; immersing the coated part of the biopsy needle in the coating solution, taking out the medical device to be loaded with drugs from the coating solution, accelerating it to below 0.1-4 cm / s, and rotating the biopsy needle horizontally at a speed of below 10-20 r / min, and giving a wind speed of 1.5-2.0 m 3 , blow dry under the condition of air temperature of 40-45℃; measure the moisture content of the drug coating and control the moisture content within the range of 2wt%-5wt%, and properly place it in a drying oven at 40-45℃ for proper drying to obtain a drug-loaded medical device with the drug coating uniformly dispersed on the surface.

[0105] In some preferred embodiments, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by spraying: controlling the temperature of the coating solution to 28-45°C, stirring the coating solution at the same time, and controlling the coating time within 6 hours; the spraying parameters include: spraying speed of 0.2-0.7 ml / min, air inlet temperature of 40-50°C, air inlet speed of 1.5-2.0 m 3 / min.

[0106] In some more preferred embodiments, in step 2, the following steps are included: applying the coating solution to the surface of the medical device to be loaded with drugs by spraying: reducing the temperature of the coating solution to 35°C-45°C, keeping it warm in a water bath, and controlling the coating time within 6 hours. The spraying parameters include: controlling the spraying speed to 0.3-0.5 ml / min, the air inlet temperature to 40-50°C, and the air inlet speed to 1.5-2.0 m / min. 3 , control the coating needle weight gain to 20-25mg / cm 2As the coating end point; measure the moisture content of the coating needle and control it within the range of 2wt%-5wt%. It can be placed in a 40-45℃ forced air drying oven for proper drying to obtain a drug-loaded medical device with the drug coating evenly dispersed on the surface.

[0107] In some more preferred embodiments, in step 2, the following steps are included: applying the inner coating solution to the surface of the medical device to be loaded with drugs by spraying: applying the inner coating: controlling the temperature of the inner coating solution to 35°C-40°C, stirring the inner coating solution, and controlling the coating time within 6 hours. The spraying parameters include: controlling the spraying speed to 0.5-0.7 ml / min, the air inlet temperature to 40-45°C, and the air inlet speed to 1.5-2.0 m 3 , control the coating needle weight gain as the coating end point, and the weight gain reaches 10-12mg / cm 2 ; Apply the outer coating solution to the surface of the drug-carrying medical device by spraying: the control parameters for applying the outer coating to the surface of the biopsy needle coated with the inner layer include: spraying speed of 0.2-0.4ml / min, air inlet temperature of 45-50℃, air inlet speed of 1.5-2.0m 3 , control the coating weight gain as the coating end point, and the weight gain reaches 18-20mg / cm 2 .

[0108] In some preferred embodiments, the friction coefficient of the drug coating is 0.4-0.6.

[0109] In some preferred embodiments, the viscosity of the coating solution prepared in step 1 is 500-5000 mPa·s.

[0110] In some further more preferred embodiments, gelatin is used as the most preferred carrier material, and other substances can be appropriately added in small amounts to improve the properties of the coating. For example, adding polyvinyl alcohol, polyacrylic acid, etc. can enhance the toughness of the drug coating, thereby improving the removability of the drug coating, slowing down the release rate of the drug in the body, and reducing the friction coefficient.

[0111] In some further more preferred embodiments, polyethylene glycol and polyvinyl alcohol are used together, which has good film-coating properties and film-forming firmness and removability, so as to meet the ideal requirements.

[0112] In the present invention, surfactants and moisturizers are substances added in trace amounts in the coating process, which can broaden the process parameters, extend the temperature range during coating and the coating time limit of the coating solution; at the same time, they can improve the moisturizing properties of the coating film and avoid problems such as cracking of the coating film due to drying.

[0113] The various substances of the present invention should have good compatibility with each other to avoid product stability problems caused by the compatibility of the materials. For example, platinum drugs (carboplatin, cisplatin, etc.) and gelatin cannot be coated together. Platinum substances can denature gelatin after being placed for a long time, resulting in problems with the release of the coating. No compatibility problems have been found between other drugs of the present invention and carrier substances.

[0114] The drug coating of the present invention has good compatibility with the human body and can be degraded in the body without causing any impact on human health.

[0115] In the present invention, the drug in the drug coating mainly plays a role in killing tumor cells; the carrier material can fix the raw drug on the biopsy needle and has a certain formability; the surfactant can improve the feasibility of the coating process, broaden the parameter range of the coating preparation method, and add the surfactant in the dip coating process, which can extend the coating time of the solution to be coated to 6-12h, and can widen the coating temperature range of the solution to be coated to 25°C-50°C. The surfactant of the present invention not only has the effect of optimizing the parameters of the coating preparation method, can increase the coating time of the solution to be coated and expand the temperature range of the coating solution when it can be coated, but also has the effect of increasing the solubility of the raw drug and thus increasing the concentration of the drug in the coating solution, increasing the drug loading after coating, and promoting the absorption of the drug in the body.

[0116] The drug coating of the present invention has multiple auxiliary therapeutic effects, and according to different types of drugs, has the effects of killing tumors, stopping bleeding, reducing inflammation, relieving pain, and promoting wound healing.

[0117] In the present invention, a carrier material with a controlled release effect, such as hydroxypropyl methylcellulose and hydroxyethyl cellulose, is added to the drug coating to improve the release rate of the drug at the target position in the body, thereby improving the effectiveness and safety of clinical use. At the same time, such a material is also a film-forming material, which can improve the firmness of the coating.

[0118] In the present invention, the carrier material can be co-dissolved or co-dispersed with the drug to form a dispersion material before coating. After the coating is dried, the drug is fully dispersed in the carrier material, which can solve the problems of the drug not being firmly combined in the coating, the drug not being evenly dispersed, the drug being released suddenly, the drug being degraded, and the coating being unevenly formed. The form in which the drug exists on the coating is changed, the firmness of the raw material on the biopsy needle is improved, and the drug is evenly dispersed on the device without affecting the release of the drug in the body.

[0119] The drug coating of the present invention has excellent firmness, can be firmly combined with the surface of the drug-carrying medical device, and will not cause the properties of the coating to change with the prolonged placement time. The excellent firmness is manifested in that the friction coefficient of the product does not change after multiple simulated punctures in vitro, and the drug coating is firmly attached to the surface of the drug-carrying medical device.

[0120] The drug coating of the present invention can reduce the friction force on the surface of the drug-carrying medical device, reduce the friction coefficient during puncture, and reduce the resistance of biopsy needle puncture.

[0121] The drug coating of the present invention can also fall off at a targeted position in the body, allowing the drug to accurately reach the targeted position, thereby achieving the function of providing drug treatment while taking a biopsy sample.

[0122] The drug coating of the present invention can improve the smoothness of the surface of the drug-carrying medical device and reduce the puncture resistance without affecting the function / performance of the original drug-carrying medical device, thereby reducing the puncture pain and increasing the applicability of clinical use.

[0123] According to the preparation method of the drug coating of the present invention, the drug coating is firmly combined with the surface of the drug-carrying medical device, can be quickly detached in the body, and the drug is released in the body, and the drug release ratio can reach more than 90%.

[0124] The drug coating of the present invention has good bonding performance with the surface of the drug-carrying medical device and has excellent firmness before use. During the stable placement process, the firmness of the bonding between the coating and the biopsy needle will not change.

[0125] In the present invention, the firmness of the drug coating can be reflected by the friction coefficient, and the firmness of the combination of the drug coating and the drug-loaded medical device can be detected and evaluated by multiple in vitro puncture tests. Through multiple in vitro puncture tests, the friction coefficients of the drug-loaded (i.e., coated) medical device and the non-drug-loaded (i.e., uncoated) medical device are measured multiple times, and then the two are compared.

[0126] In the preparation process of the drug coating of the present invention, moisture control is also an important factor to ensure the firmness of the coating, and the moisture of the coating should be controlled within 2 wt%-5 wt%. Under the premise of moisture control, the coating has good firmness in vitro and will not fall off after multiple punctures in vitro; when simulating the clinical use of the coated puncture needle to puncture in vitro tissues or biological organs, it can fall off completely under the temperature and body fluid environment of the punctured organism.

[0127] In the preparation process of the drug coating of the present invention, 95%-98% of the solvent is removed, and the solvent content in the finally prepared drug coating is 2 wt%-5 wt%.

[0128] The preparation process of the drug coating of the present invention includes dissolving the drug and the carrier material in a solvent, so that the drug is molecularly dispersed in the carrier material, adding a surfactant to the solvent, and increasing the control range of the coating temperature and the time for coating in the coating process.

[0129] In some preferred embodiments, during the preparation of the drug coating, the solvent that dissolves the drug is used as a humectant for the controlled release material, the controlled release material is dispersed, and then the coating is performed by spraying.

[0130] In the preparation process of the drug coating of the present invention, it is necessary to control the concentration of the carrier substance and the drug concentration in the coating solution, and to control the temperature of the coating solution in the coating process. The temperature during the coating process is 25°C-50°C. It is also necessary to control the solvent content of the coating after drying. The solvent is controlled between 2wt%-5wt%, which can effectively ensure the firmness of the combination of the coating and the biopsy needle, and can also ensure that the coating is effectively detached during the puncture process, thereby obtaining good product stability and effectiveness in clinical use.

[0131] The number of drug coating layers on the surface of the drug-carrying medical device of the present invention can be designed in various ways according to the use requirements, and the drug coating layer is at least one layer.

[0132] In the preparation process of the drug coating of the present invention, the effect of compound drug loading can be achieved by coating with multiple layers, such as two layers, three layers, four layers, etc. The multilayer coating of the drug coating of the present invention can be optimized and combined according to the drug interaction and the stability of the drug. In some preferred embodiments, the drug coating includes two layers, the inner layer includes the first drug, and the outer layer (i.e., the drug coating directly in contact with the punctured body tissue) includes the second drug. In some preferred embodiments, the drug coating includes four layers, wherein the first coating does not contain a drug, the second coating contains the first drug, the third coating contains the second drug, and the fourth coating does not contain a drug as a protective outer layer (i.e., the drug coating directly in contact with the punctured body tissue).

[0133] As the number of coating layers increases, the surface thickness or diameter of the drug-coated medical device for puncture will increase. Generally, one to three layers are preferred to achieve the compound drug-loading effect.

[0134] In some preferred embodiments of the present invention, for drug coatings comprising at least two layers, in the multi-layer coating process, the innermost layer coating process is spraying or dipping, and the outer layer coating process is spraying. The re-coating of the coated drug-loaded medical device must adopt the spraying process, which is less likely to affect the properties of the inner layer coating.

[0135] The drug coating of the present invention is a solid dispersion, which can change the dispersion form of the drug in the coating. After the drug and the carrier material are co-dissolved, they are dried to form a coating. The drug is first dispersed in the form of molecules and then forms a mixture with the carrier material.

[0136] The drug coating of the present invention has the characteristic of a smooth surface. If applied to drug-loaded medical devices (such as biopsy needles and ablation needles) for puncturing the body tissue of a subject, it can reduce puncture resistance in clinical applications, and can reduce puncture pain and increase puncture adaptability compared to biopsy needles without a coating.

[0137] The drug coating of the present invention has the characteristics of directional shedding and drug release. First, it can form a firm coating on the surface of the drug-carrying medical device, which will not fall off in vitro; when the drug-carrying medical device enters the body, the coating can be effectively shed under the influence of the in vivo environment; while the drug coating is shedding, the shed drug coating can be degraded in the body, and the drug is released in the body.

[0138] The drug coating of the present invention also has the characteristic of controlled release of drugs in vivo. By controlling the difference of coating materials, the release rate of drugs in vivo is 0.2 mg / h-18 mg / h.

[0139] In order to make the purpose, technical scheme and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. The experimental methods in the following embodiments where specific conditions are not specified are usually tested under conventional conditions or under conditions recommended by the manufacturer, and the chemicals are all commercially available.

[0140] The following chemicals are included in the raw materials of the following examples and comparative examples:

[0141] The molecular weight of gelatin is 30000-300000. When the concentration is 6.67%, the viscosity of gelatin is 2-5mPa·s at 60°C. When the concentration is 0.5%, the viscosity is 50-500mPa·s at 30°C, which is of pharmaceutical grade.

[0142] Polyvinyl alcohol, average molecular weight of 16000-20000, viscosity of 20.0-30.0mPa·s, water-soluble, medical grade.

[0143] Polyethylene glycol 4000, with an average molecular weight of about 4000, has a viscosity of 50-250 mPa·s at 30°C when the concentration is 0.5%, which is of pharmaceutical grade.

[0144] Polyacrylic acid, when the concentration in the solution is 15%-25%, the molecular weight is 500-5000, the viscosity is 10000-20000mPa·s, when the concentration is 0.5%, at 30℃, the viscosity is 1500-2000mPa·s, which is medical grade.

[0145] Tween 60 and / or Tween 80, viscosity 200-800mPa·s, average molecular weight 200-600, pharmaceutical grade.

[0146] The test items for properties, firmness, shedding, friction coefficient, stability, drug release and other characteristics of the samples in the following examples or comparative examples are shown in Table 1 below.

[0147] Table 1 Test items of samples in examples or comparative examples

[0148] Test items Detection Methods Eligibility criteria Characteristics Visual inspection The coating surface is uniform, without dents, protrusions or cracks Coating fastness After puncturing the silicone material 15 times in vitro, the surface properties of the coating were observed and the friction coefficient was measured After puncturing 15 times, the coating surface should be uniform, without depressions, protrusions or cracks, and the friction coefficient should not exceed 1. Shedding Puncture the ex vivo tissue, wait for 5 minutes after puncture, remove the biopsy needle, and measure the drug residue in the biopsy needle (%) The drug residue in the biopsy needle after puncture should not exceed 10%, ensuring that more than 90% of the drug falls off at the target site Friction coefficient After puncturing the silicone material 10 times in vitro, the friction coefficient was measured 5 times in succession The coefficient of friction should not exceed 1. stability After the coated biopsy needles were placed at a temperature of 30°C and a humidity of 65%RH for 6 months, the firmness and shedding of the coated biopsy needles were measured. After being placed at a temperature of 30°C and a humidity of 65%RH for 6 months, the firmness of the coated biopsy needle should meet the requirements, and the shedding should meet the requirements. In vitro drug release The dissolution medium is water or water containing 0.1% sodium dodecyl sulfate, the volume is 250 ml, the rotation speed is 75 rpm, and the time is 15 min. The cumulative release rate of the drug is measured. The cumulative release rate of the drug should be above 90% Example 1

[0149] The component table is shown in Table 2 below:

[0150] Table 2 Components of Example 1

[0151] type Dosage percentage effect Gemcitabine Hydrochloride 2g 16.4% Active ingredients in medicines that provide therapeutic effects gelatin 10g 82.0% Carrier material, providing drug loading function Twain 80 0.1g 0.8% Surfactants, improve preparation process and promote drug absorption Carmine 0.1g 0.8% Color enhancer, convenient for subsequent test observation Water for injection 87.8g / Solvents, used in the preparation process, are mostly removed in the end

[0152] The preparation method of the drug coating comprises:

[0153] (1) Take 10 g of gelatin, add it to a beaker, add 87.9 g of water for injection, use a water bath magnetic stirrer, set the stirring speed to 75 r / min, make the solution have a slight vortex, stir it in a water bath at 60°C to dissolve the gelatin, cool the solution to 40°C, and set aside;

[0154] (2) Add 0.1 g Tween 80 and 0.1 g carmine to the above solution, stir evenly and set aside;

[0155] (3) adding 2 g of gemcitabine hydrochloride, stirring to dissolve, mixing evenly to obtain a clear and transparent solution, preparing a coating solution, cooling to 30° C., and having a viscosity of 3765 mPa·s;

[0156] (4) Applying the coating: applying the coating solution to the surface of the biopsy needle to be loaded with the drug by dipping: controlling the temperature of the coating solution to 30°C-32°C, keeping it warm in a water bath, and controlling the coating time within 8 hours, immersing the coated part of the biopsy needle in the coating solution, lifting the biopsy needle out of the coating solution, accelerating it to 1.2 cm / s, and rotating the biopsy needle horizontally at a speed of 15 r / min, so that the coating solution decreases with the temperature and the water evaporates, and the coating solution is evenly dispersed on the surface of the biopsy needle, and after the water evaporates by 50%, the intermediate product of the drug-loaded biopsy needle is obtained;

[0157] (5) The intermediate product of the drug-loaded biopsy needle is placed at 40° C. and dried for 15 minutes, and the moisture content is controlled within the range of 2wt%-5wt%, thereby obtaining a drug-loaded biopsy needle with the drug coating uniformly dispersed on the surface.

[0158] Test items: In this embodiment, the dissolution medium in the drug release test item is water, and the others are as shown in Table 1.

[0159] The test results are shown in Table 3 below:

[0160] Table 3 Test results of Example 1

[0161] Test items Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 average value Characteristics Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Coating fastness The coating surface meets the requirements and the friction coefficient is 0.56 The coating surface meets the requirements and the friction coefficient is 0.45 The coating surface meets the requirements and the friction coefficient is 0.48 The coating surface meets the requirements and the friction coefficient is 0.46 The coating surface meets the requirements and the friction coefficient is 0.53 The coating surface meets the requirements and the friction coefficient is 0.58 The coating surface meets the requirements, and the average friction coefficient is 0.51 Shedding 5 6 5 5 6 5 5.3 Friction coefficient 0.54 0.56 0.48 0.46 0.46 0.54 0.51 stability Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Drug release% 95 96 93 95 95 94 94.6

[0162] Analysis of results: In the preparation method of Example 1, a dip coating method is adopted to prepare a product with a coating layer. During the preparation process, parameters such as temperature are focused on control. All indicators of the prepared product are in line with expectations, and the coating has obvious coating firmness. The product can ensure that the coating will not fall off or change during the stability placement process and before use, and has the property of falling off during use. When the product is used, under the influence of the body temperature and body fluid environment of the punctured body tissue, the coating can fall off, allowing the drug to reach the target position. At the same time, it has the function of reducing friction, which can reduce the resistance to puncture and make puncture easier. Example 2

[0163] The component table is shown in Table 4 below:

[0164] Table 4 Components of Example 2

[0165] type Dosage percentage effect Paclitaxel 0.3g 1.9% Active ingredients in medicines that provide therapeutic effects gelatin 15g 97.4% Carrier material, providing drug loading function Twain 80 0.1g 0.6% Surfactants, improve preparation process and promote drug absorption Anhydrous ethanol 10g / Solvents, used in the preparation process, are mostly removed in the end Water for injection 74.6g / Solvents, used in the preparation process, are mostly removed in the end

[0166] The preparation method of the drug coating comprises:

[0167] (1) Take 10 g of gelatin, add it to a beaker, add 74.6 g of water for injection, use a water bath magnetic stirrer, set the stirring speed to 100 r / min, make the solution have a slight vortex, stir it in a water bath at 60°C to dissolve the gelatin, cool the solution to 38°C, and set aside;

[0168] (2) Add 0.1 g of Tween 80 to the above solution, stir evenly and set aside;

[0169] (3) Take 0.3 g of paclitaxel, add it to a beaker, add 10 g of anhydrous ethanol, and stir to dissolve it;

[0170] (4) Mix the above two solutions, control the temperature at 40°C-45°C in a closed container, stir them thoroughly, mix them evenly, obtain a clear and transparent solution, and prepare a coating solution, cool it to 30°C, and the viscosity is 2875mPa·s;

[0171] (5) Applying the coating: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: controlling the temperature of the coating solution to 32°C-34°C, keeping it warm in a water bath, controlling the coating time to be within 8 hours, immersing the coated part of the biopsy needle in the coating solution, increasing the speed by 0.3 cm / s, and rotating the biopsy needle horizontally at a speed of 10 r / min, so that the coating solution decreases with the temperature and the water evaporates, and the coating solution is evenly dispersed on the surface of the biopsy needle, and after the water evaporates by 60%, the intermediate product of the drug-loaded biopsy needle is obtained;

[0172] (6) The intermediate product of the drug-loaded biopsy needle is placed at 40° C. and dried for 15 min, and the moisture content is controlled within the range of 2wt%-5wt%, thereby obtaining a drug-loaded biopsy needle with the drug coating uniformly dispersed on the surface.

[0173] Test items: In this embodiment, the dissolution medium in the drug release test item is water containing 0.1% sodium dodecyl sulfate, and the others are as shown in Table 1.

[0174] The test results are shown in Table 5 below:

[0175] Table 5 Test results of Example 2

[0176] Test items Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 average value Characteristics Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Coating fastness The coating surface should meet the requirements, and the friction coefficient is 0.41 The coating surface should meet the requirements, with a friction coefficient of 0.45 The coating surface should meet the requirements, with a friction coefficient of 0.42 The coating surface should meet the requirements, with a friction coefficient of 0.43 The coating surface should meet the requirements, with a friction coefficient of 0.43 The coating surface should meet the requirements and the friction coefficient should be 0.50 The coating surface should meet the requirements, and the average friction coefficient is 0.44 Shedding situation (%) 3 4 5 4 5 5 4.3 Friction coefficient 0.44 0.46 0.40 0.46 0.42 0.44 0.44 stability Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Drug release (%) 96 97 93 94 93 96 94.8

[0177] Result analysis: In the preparation method of Example 2, a dip-coating method is adopted to prepare a product with a coating layer. Anhydrous ethanol is introduced into the components of this example as a solubilizer to dissolve the drug paclitaxel. All indicators of the prepared product meet the requirements and have obvious coating firmness. The product can ensure that the coating will not fall off or change during the stability placement process and before use, and has the property of falling off during use. When the product is used, under the influence of the body temperature and body fluid environment of the punctured body tissue, the coating can fall off, allowing the drug to reach the target position. At the same time, it has the function of reducing friction, which can reduce the resistance of puncture and make puncture easier. Example 3

[0178] The component table is shown in Table 6 below:

[0179] Table 6 Components of Example 3

[0180] type Dosage percentage effect Fluorouracil 0.5g 3.6% Active ingredients in medicines that provide therapeutic effects Polyvinyl alcohol 3g 21.9% Carrier material, providing drug loading function gelatin 10g 73% Carrier material, providing drug loading function Twain 80 0.1g 0.7% Surfactants, improve preparation process and promote drug absorption glycerin 0.1g 0.7% Moisturizer, improves cracking of long-term storage coating Water for injection 86.3g / Solvents, used in the preparation process, are mostly removed in the end

[0181] The preparation method of the drug coating comprises:

[0182] (1) Disperse 3 g of polyvinyl alcohol in 86.2 g of water for injection overnight to dissolve the polyvinyl alcohol completely;

[0183] (2) Take 10 g of gelatin and add it to the above polyvinyl alcohol solution. Use a water bath magnetic stirrer and set the stirring speed to 150 r / min to make the solution slightly vortex. Stir it in a water bath at 60°C to dissolve the gelatin. Cool the solution to 35°C and set aside.

[0184] (3) Add 0.1 g of Tween 80 and 0.1 g of glycerol to the above solution, control the stirring speed so that bubbles are not generated, stir thoroughly and set aside;

[0185] (4) 0.5 g of fluorouracil was slowly added to the above solution, stirred to dissolve, and mixed evenly to obtain a clear and transparent solution to prepare a coating solution. When the temperature was lowered to 30° C., the viscosity was 4480 mPa·s;

[0186] (5) Applying the coating: applying the coating solution to the surface of the medical device to be loaded with drugs by spraying: raising the temperature of the coating solution to 40°C-45°C, keeping it warm in a water bath, and controlling the coating time within 6 hours. The spraying parameters include: controlling the spraying speed to 0.4 ml / min, the air inlet temperature to 45°C, and the air inlet speed to 1.6 m / min. 3 , control the coating needle weight gain to 23mg / cm 2 As coating endpoint;

[0187] (6) Determine the moisture content of the coated needle. Place the needle in a 40°C forced air drying oven and dry it appropriately. Control the moisture content within the range of 2wt%-5wt% to obtain a drug-loaded biopsy needle with the drug coating evenly dispersed on the surface.

[0188] Test items: In this embodiment, the dissolution medium in the drug release test item is water containing 0.1% sodium dodecyl sulfate, and the others are as shown in Table 1.

[0189] The test results are shown in Table 7 below:

[0190] Table 7 Test results of Example 3

[0191] Test items Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 average value Characteristics Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Coating fastness The coating surface meets the requirements and the friction coefficient is 0.31 The coating surface meets the requirements and the friction coefficient is 0.31 The coating surface meets the requirements and the friction coefficient is 0.32 The coating surface meets the requirements and the friction coefficient is 0.30 The coating surface meets the requirements and the friction coefficient is 0.33 The coating surface meets the requirements and the friction coefficient is 0.40 The coating surface meets the requirements, and the average friction coefficient is 0.33 Shedding situation (%) 5 6 6 6 7 6 6 Friction coefficient 0.34 0.33 0.30 0.32 0.33 0.35 0.33 stability Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Drug release (%) 96 98 95 96 97 98 96.7

[0192] Result analysis: Example 3 adds glycerin as a humectant based on Example 1 and Example 2, which can avoid problems such as coating cracking caused by improper storage of the product.

[0193] By adding glycerol to the components of Example 3, problems are less likely to occur due to improper moisture control in the last step. All indicators of the prepared product meet the requirements and have obvious coating firmness. The product can ensure that the coating will not fall off or change during the stability placement process and before use. At the same time, it has the property of falling off during use. When the product is used, under the influence of the body temperature and body fluid environment of the punctured body tissue, the coating can fall off, allowing the drug to reach the target position. At the same time, it has the function of reducing friction, which can reduce the resistance to puncture and make puncture easier. Example 4

[0194] The component table is shown in Table 8 below:

[0195] Table 8 Components of Example 4

[0196] type Dosage percentage effect Levofloxacin Hydrochloride 3g 19.8% Active ingredients in medicines that provide therapeutic effects gelatin 11g 72.8% Carrier material, providing drug loading function Polyacrylic acid 1g 6.6% Carrier material, providing drug loading function Twain 60 0.1g 0.7% Surfactants, improve preparation process and promote drug absorption Water for injection 84.9g / Solvents, used in the preparation process, are mostly removed in the end

[0197] The preparation method of the drug coating comprises:

[0198] (1) Disperse 1 g of polyacrylic acid in 84.9 g of water for injection and stir to dissolve it;

[0199] (2) Take 3 g of levofloxacin hydrochloride, slowly add it to the above solution, and stir to dissolve it;

[0200] (3) Take 11 g of gelatin and add it to the above solution. Use a water bath magnetic stirrer and set the stirring speed to 100 r / min to make the solution vortex slightly. Stir it in a water bath at 60°C to dissolve the gelatin. Cool the solution to 40°C and set aside.

[0201] (4) Add 0.1 g of Tween 60 to the above solution, control the stirring speed so that bubbles are not generated, stir thoroughly, mix evenly, and obtain a clear and transparent solution to prepare a coating solution with a viscosity of 3230 mPa·s;

[0202] (5) Applying the coating: applying the coating solution to the surface of the medical device to be loaded with drugs by dipping: including lowering the temperature of the coating solution to 28°C-30°C and controlling the coating time within 12 hours; immersing the coated part of the biopsy needle in the coating solution, lifting the biopsy needle out of the coating solution, increasing the speed by 2 cm / s, and rotating the biopsy needle horizontally at a speed of 10 r / min, and applying a wind speed of 1.8 m / s. 3 , blow dry at a wind temperature of 42°C;

[0203] (6) Determine the moisture content of the drug coating, place it in a 40° C. forced air drying oven and properly dry it to control the moisture content within the range of 2 wt %-5 wt %, thereby obtaining a drug-loaded biopsy needle with the drug coating evenly dispersed on the surface.

[0204] Test items: In this embodiment, the dissolution medium in the drug release test item is water containing 0.1% sodium dodecyl sulfate, and the others are as shown in Table 1.

[0205] The test results are shown in Table 9 below:

[0206] Table 9 Test results of Example 4

[0207] Test items Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 average value Characteristics Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Coating fastness The coating surface meets the requirements and the friction coefficient is 0.41 The coating surface meets the requirements and the friction coefficient is 0.43 The coating surface meets the requirements and the friction coefficient is 0.44 The coating surface meets the requirements and the friction coefficient is 0.50 The coating surface meets the requirements and the friction coefficient is 0.42 The coating surface meets the requirements and the friction coefficient is 0.38 The coating surface meets the requirements, with an average friction coefficient of 0.43 Shedding situation (%) 2 3 3 4 3 2 2.8 Friction coefficient 0.44 0.38 0.40 0.50 0.48 0.37 0.43 stability Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Drug release (%) 97 98 96 97 97 95 96.7

[0208] Result analysis: The drug used in Example 4 has a high solubility, accounting for nearly 20%, and a clear solution to be coated can still be obtained. The firmness, removability, drug release rate and stability of the coated product are all excellent.

[0209] All indicators of the product prepared in Example 4 meet the requirements, and the product has obvious coating firmness. The product can ensure that the coating will not fall off or change during the stability placement process and before use. At the same time, it has the property of falling off during use. When the product is used, under the influence of the body temperature and body fluid environment of the punctured body tissue, the coating can fall off, allowing the drug to reach the target position. At the same time, it has the function of reducing friction, which can reduce the resistance to puncture and make puncture easier. Example 5

[0210] The component table is shown in Table 10 below:

[0211] Table 10 Components of Example 5

[0212]

[0213] The preparation method of the drug coating comprises:

[0214] 1. Preparation of inner coating:

[0215] (1) Take 10 g of gelatin, add it to a beaker, add 89.75 g of water for injection, use a water bath magnetic stirrer, set the stirring speed to 120 r / min, make the solution have a slight vortex, stir it in a water bath at 60°C to dissolve the gelatin, cool the solution to 40°C, and set aside;

[0216] (2) Add 0.05 g of Tween 80 to the above solution, control the stirring speed so that bubbles are not generated, stir thoroughly, mix well, and set aside;

[0217] (3) Take 0.1 g of paclitaxel and add it to a beaker. Add 10 g of anhydrous ethanol to the beaker and stir to dissolve it.

[0218] (4) The two solutions are mixed and stirred to obtain a clear and transparent solution, and an inner coating solution is obtained. When the temperature is 30° C., the viscosity is 3478 mPa·s;

[0219] (5) Applying the inner coating: applying the inner coating solution to the surface of the medical device to be loaded with drugs by spraying: controlling the temperature of the inner coating solution to 35°C-40°C, stirring the inner coating solution, and controlling the coating time within 6 hours. The spraying parameters include: controlling the spraying speed to 0.6 ml / min, the air inlet temperature to 40°C, and the air inlet speed to 1.7 m / min. 3 , control the coating needle weight gain to 11mg / cm 2 As coating endpoint;

[0220] 2. Preparation of outer coating:

[0221] (1) Take 1 g of polyvinyl alcohol and add it to a beaker. Then take 90.4 g of water for injection and add it to the beaker. Stir to disperse the polyvinyl alcohol. Leave overnight to allow the polyvinyl alcohol to fully dissolve.

[0222] (2) Take 8 g of polyethylene glycol 4000, add it to the polyvinyl alcohol solution, and stir to dissolve the polyethylene glycol;

[0223] (3) Take 0.5 g of ethylphenolsulfonamide, add it to the above solution, and stir to dissolve it;

[0224] (4) Take 0.1 g of glycerol and add it to the above solution, stir to mix it evenly, control the stirring speed so that no bubbles appear, stir thoroughly to obtain a clear and transparent solution, and prepare an outer coating solution with a viscosity of 698 mPa·s;

[0225] (5) Applying the outer coating: applying the outer coating solution to the surface of the drug-carrying medical device by spraying: including applying the outer coating to the surface of the biopsy needle coated with the inner layer. The control parameters include: spraying speed of 0.3 ml / min, air inlet temperature of 50°C, air inlet speed of 1.7 m / min. 3 , control the coating weight gain to 19mg / cm 2 as coating end point.

[0226] Test items: In this embodiment, the dissolution medium in the drug release test item is water containing 0.1% sodium dodecyl sulfate, and the others are as shown in Table 1.

[0227] The test results are shown in Table 11 below:

[0228] Table 11 Test results of Example 5

[0229] Test items Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 average value Characteristics Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Coating fastness The coating surface meets the requirements and the friction coefficient is 0.61 The coating surface meets the requirements and the friction coefficient is 0.61 The coating surface meets the requirements and the friction coefficient is 0.52 The coating surface should meet the requirements, with a friction coefficient of 0.60 The coating surface meets the requirements and the friction coefficient is 0.53 The coating surface meets the requirements and the friction coefficient is 0.50 The coating surface meets the requirements, and the average friction coefficient is 0.56 Outer layer shedding condition (% residual ethamine) 0 0 1 0 0 0 0.16 Inner layer shedding (paclitaxel residue %) 6 7 7 8 6 7 6.8 Friction coefficient 0.51 0.52 0.50 0.60 0.53 0.55 0.53 stability Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Comply with regulations Outer layer drug release (ethylamine) % 100 99 99 98 100 100 99.3 Inner layer drug release (paclitaxel) % 95 94 94 93 92 95 93.8

[0230] Result analysis:

[0231] In Example 5, the coating process of both layers adopts the spraying method. All indicators of the prepared product meet the requirements and have obvious coating firmness. The product can ensure that the coating will not fall off or change during the stability placement process and before use. At the same time, it has the property of falling off during use. When the product is used, under the influence of the body temperature and body fluid environment of the punctured body tissue, the coating can fall off, allowing the drug to reach the target position. At the same time, it has the function of reducing friction, which can reduce the resistance to puncture and make puncture easier. Comparative Example 1

[0232] The component table is shown in Table 12 below:

[0233] Table 12 Components of Comparative Example 1

[0234] type Dosage percentage effect Fluorouracil 0.5g 9% Active ingredients in medicines that provide therapeutic effects Xanthan gum 2g 91% Carrier material, providing drug loading function Water for injection 97.5g / Solvents, used in the preparation process, are mostly removed in the end

[0235] The preparation method of the drug coating comprises:

[0236] (1) Take 0.5 g of fluorouracil and add it to a beaker. Add 94.5 g of water for injection and use a water bath magnetic stirrer. Set the stirring speed to 60 r / min to make the solution vortex slightly and stir until it dissolves.

[0237] (2) Take 5 g of xanthan gum and add it to the above solution. Use a water bath magnetic stirrer and set the stirring speed to 100 r / min to make the solution slightly vortex. Stir it in a water bath at 60°C. The xanthan gum dissolves slowly. Cool it to room temperature overnight. The xanthan gum is completely dissolved to obtain a clear coating solution. The viscosity is 22080 mPa·s.

[0238] (3) Coating: The temperature of the coating solution is controlled at 40° C.-45° C., and the coating time is controlled within 8 hours. The coating is performed by dipping, and the coated part of the biopsy needle is immersed in the coating solution. The biopsy needle is lifted out of the coating solution, and the speed is increased by 4 cm / s. The biopsy needle is rotated horizontally at a speed of 10 r / min, so that the coating solution is cooled down and the water evaporates. The coating solution is evenly dispersed on the surface of the biopsy needle. After the water evaporates by 60%, the intermediate product of the drug-loaded biopsy needle is obtained.

[0239] (4) The intermediate product of the drug-loaded biopsy needle is placed at 40° C. and dried for 15 minutes, and the moisture content is controlled within the range of 2wt%-5wt%, thereby obtaining a drug-loaded biopsy needle.

[0240] Test items: In this comparative example, the dissolution medium in the drug release test item is water, and the others are as shown in Table 1.

[0241] The test results are shown in Table 13 below:

[0242] Table 13 Test results of comparative example 1

[0243]

[0244] Result analysis: Comparative Example 1 uses different carrier materials, and the difficulty of the coating process during the coating preparation process is different. The viscosity of the coating solution reaches 22080mPa·s. The viscosity of the coating solution is too large, and the solution cannot be sprayed, so only the dipping process can be used; during the dipping process, the coating surface is uneven due to the high viscosity of the coating solution. In this comparative example 1, a single xanthan gum is selected as the carrier material, and the coating can be implemented. After preparation, the coating has better firmness, and the coating does not fall off after multiple punctures, but the shedding property of the coating is poor, and the drug does not fall off after puncture. The reason for the analysis should be: the nature of xanthan gum cannot be quickly dissolved under suitable temperature and body fluid environment. Comparative Example 2

[0245] The component table is shown in Table 14 below:

[0246] Table 14 Components of Comparative Example 2

[0247] type Dosage percentage effect Gemcitabine Hydrochloride 5g 33.1% Active ingredients in medicines that provide therapeutic effects gelatin 10g 66.2% Carrier material, providing drug loading function Twain 80 0.1g 0.6% Surfactants, improve preparation process and promote drug absorption Water for injection 84.9g / Solvents, used in the preparation process, are mostly removed in the end

[0248] The preparation method of the drug coating comprises:

[0249] (1) Take 10 g of gelatin, add it to a beaker, add 84.9 g of water for injection, use a water bath magnetic stirrer, set the stirring speed to 75 r / min, make the solution have a slight vortex, stir it in a water bath at 60°C to dissolve the gelatin, cool the solution to 40°C, and set aside;

[0250] (2) Add 0.1 g Tween 80 to the above solution, stir well and set aside.

[0251] (3) Add 5 g of gemcitabine hydrochloride and stir thoroughly until the drug cannot be completely dissolved to obtain a coating suspension;

[0252] (4) Coating: The temperature of the coating solution is controlled to be 28°C-35°C, and the solution is kept warm in a water bath, preferably at 30°C-32°C. The coating time is controlled within 8 hours. During the coating process, the solution is slightly stirred at a stirring speed of 25 r / min to avoid drug precipitation. The coating is performed by dipping, and the coated part of the biopsy needle is immersed in the coating solution. The biopsy needle is lifted out of the coating solution, the speed is increased by 1.0 cm / s, and the biopsy needle is rotated horizontally at a speed of 15 r / min, so that the coating solution decreases with the temperature and the water evaporates. The coating solution is evenly dispersed on the surface of the biopsy needle. After the water evaporates by 60%, the drug-loaded biopsy needle intermediate product is obtained;

[0253] (5) The intermediate product of the drug-loaded biopsy needle is placed at 40° C. and dried for 15 minutes, and the moisture content is controlled within the range of 2wt%-5wt%, thereby obtaining a drug-loaded biopsy needle.

[0254] Test items: In this comparative example, the dissolution medium in the drug release test item is water, and the others are as shown in Table 1.

[0255] The test results are shown in Table 15 below:

[0256] Table 15 Test results of comparative example 2

[0257]

[0258] Result analysis: Comparative Example 2 uses the same preparation method as Example 1, but the proportion of the drug is greater than that of Example 1, and the drug is partially undissolved in the coating solution. The coating solution is a suspension, resulting in the properties after coating not meeting the requirements. After the coating is dried, the friction coefficient increases significantly, resulting in the product not meeting the requirements. This is mainly because the insoluble drug forms tiny depressions and protrusions on the coating surface, resulting in increased friction on the surface, and the friction coefficient test results do not meet the requirements. According to this comparative example 2, the coating solution should be in a uniform solution state to ensure that the properties of the coating surface meet the requirements. Comparative Example 3

[0259] The component table is shown in Table 16 below:

[0260] Table 16 Components of Comparative Example 3

[0261] type Dosage percentage effect Fluorouracil 0.5g 9.0% Active ingredients in medicines that provide therapeutic effects Polyoxyl stearate 5g 90.1% Carrier material, providing drug loading function Twain 80 0.05g 0.9% Surfactants, improve preparation process and promote drug absorption Water for injection 94.45g / Solvents, used in the preparation process, are mostly removed in the end

[0262] The preparation method of the drug coating comprises:

[0263] (1) Take 0.5 g of fluorouracil, add it to a beaker, add 94 g of water for injection, use a water bath magnetic stirrer, set the stirring speed to 120 r / min, make the solution vortex slightly, dissolve it completely, and set aside;

[0264] (2) Add 0.5 g of stearic acid polyoxyethylene to the above solution, control the temperature at 60-65° C., stir to dissolve, then add 0.05 g of Tween 80, stir to dissolve, and set aside;

[0265] (3) Coating: The temperature of the coating solution is controlled at 40°C-42°C and kept warm in a water bath. The coating time is controlled within 12 hours. During the coating process, the solution is slightly stirred at a stirring speed of 25 r / min to avoid drug precipitation. The coating is performed by dipping. The coated part of the biopsy needle is immersed in the coating solution. The biopsy needle is lifted out of the coating solution, the speed is increased by 1.5 cm / s, and the biopsy needle is rotated horizontally at a speed of 10 r / min. The coating solution is cooled and the water evaporates as the temperature decreases. The coating solution is evenly dispersed on the surface of the biopsy needle. After the water evaporates by 50%, the drug-loaded biopsy needle intermediate product is obtained.

[0266] (4) The intermediate product of the drug-loaded biopsy needle is placed at 30° C. and dried for 2 h, and the moisture content is controlled within the range of 2 wt %-5 wt % to obtain a drug-loaded biopsy needle.

[0267] Test items: In this comparative example, the dissolution medium in the drug release test item is water, and the others are as shown in Table 1.

[0268] The test results are shown in Table 17 below:

[0269] Table 17 Test results of comparative example 3

[0270]

[0271] Analysis of results: The carrier material used in Comparative Example 3 is polyoxyl stearate. After the coating is dried, the coating has wax-like properties and a smooth surface, but lacks the cohesive force of the film material and is soft. In the in vitro simulated puncture experiment, it can be observed with the naked eye that part of the coating has fallen off. The properties of the carrier material are not appropriately selected. It can be seen that improper selection of the carrier material will result in insufficient coating firmness. Comparative Example 4

[0272] The component table is shown in Table 18 below:

[0273] Table 18 Components of Comparative Example 4

[0274] type Dosage percentage effect Carboplatin 2g 16.5% Active ingredients in medicines that provide therapeutic effects gelatin 10g 82.6% Carrier material, providing drug loading function Twain 80 0.1g 0.8% Surfactants, improve preparation process and promote drug absorption Water for injection 87.9g / Solvents, used in the preparation process, are mostly removed in the end

[0275] The preparation method of the drug coating comprises:

[0276] (1) Take 10 g of gelatin, add it to a beaker, add 87.9 g of water for injection, use a water bath magnetic stirrer, set the stirring speed to 100 r / min, make the solution have a slight vortex, stir it in a water bath at 60°C to dissolve the gelatin, cool the solution to below 40°C, and set aside;

[0277] (2) Add 0.1 g of Tween 80 to the above solution, stir evenly and set aside;

[0278] (3) adding 2 g of carboplatin and stirring to dissolve it to obtain a clear and transparent solution to prepare a coating solution;

[0279] (4) Coating: The temperature of the coating solution is controlled at 30°C-32°C, and the coating solution is kept warm in a water bath. The coating time is controlled within 8 hours. The coating is performed by dipping. The coated part of the biopsy needle is immersed in the coating solution. The biopsy needle is lifted out of the coating solution, and the speed is increased by 2.0 cm / s. The biopsy needle is rotated horizontally at a speed of 15 r / min. The coating solution is evenly dispersed on the surface of the biopsy needle as the temperature decreases and the water evaporates. After the water evaporates by 60%, the drug-loaded biopsy needle intermediate product is obtained.

[0280] (5) The intermediate product of the drug-loaded biopsy needle is placed at 40° C. and dried for 15 minutes, and the moisture content is controlled within the range of 2wt%-5wt%, thereby obtaining a drug-loaded biopsy needle.

[0281] Test items: In this comparative example, the dissolution medium in the drug release test item is water, and the others are as shown in Table 1.

[0282] The test results are shown in Table 19 below:

[0283] Table 19 Test results of comparative example 4

[0284]

[0285] Result analysis: except for the different drugs, this comparative example uses the same components and preparation process as Example 1, and all indicators of the prepared products meet the requirements. The coating has good firmness and good shedding performance, and the friction coefficient also meets the requirements.

[0286] However, during the stability test, the coating was not completely detached. The coating still had excellent firmness, but the drug could not be fully released. The main reason was that the properties of the carrier material changed. In Comparative Example 4, the drug caused the properties of the carrier material to change, and the initial properties were lost, resulting in the problem of unqualified products after stability was tested.

[0287] The present invention takes into account the interaction between the drug and the excipients, avoids the incompatibility between the drug and the excipients, and prevents changes in the carrier properties that lead to changes in the drug release degree, firmness or shedding properties.

[0288] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and do not constitute a limitation on the content of the present invention. Although the present invention has been listed in detail through the above embodiments, those skilled in the art can still make various changes in form and details according to the technical contents described in the summary of the invention and the embodiment part, without departing from the spirit and scope of the present invention defined by the attached claims.

Claims

1. A drug coating, characterized in that: Based on the total mass of raw materials, Includes the following components: 0.1 wt%-29.9 wt% drug, 70 wt%-99 wt% carrier material and 0.01 wt%-5 wt% surfactant; The drug includes at least one of an anticancer drug, an antibacterial and anti-inflammatory drug, a hemostatic drug, and an analgesic drug; The anticancer drug comprises at least one of fluorouracil, paclitaxel, bleomycin, epirubicin, gemcitabine hydrochloride, mitoxantrone hydrochloride, ifosfamide, elenin, and bortezomib; The antibacterial and anti-inflammatory drugs include at least one of tigecycline, minocycline, doxycycline, metacycline, demeclocycline, tetracycline, oxytetracycline, chloramphenicol, thiamphenicol, norfloxacin, ciprofloxacin, ofloxacin, levofloxacin hydrochloride, lomefloxacin, fleroxacin, sparfloxacin, ampicillin, amoxicillin, carbenicillin, piperacillin, cephalothin, cefazolin, ceftriaxone, cefapirin, ceftriaxone, cefuroxime axetil, and cefuroxime sodium; The hemostatic drug includes at least one of ethidiumsulfonate, thrombin, desmopressin, vitamin K1, vitamin K3, vitamin K4, fibrinogen, tranexamic acid, aminoacetic acid, aminobenzoic acid, aprotinin, carbaclorol, and carbazochrome sodium sulfonate; Analgesics included at least one of acetaminophen, ibuprofen, codeine, tramadol, morphine, fentanyl, hydromorphone, gabapentin, and pregabalin; The carrier material comprises at least one of gelatin, sodium polyacrylate, polyacrylic acid, polyvinyl alcohol, sodium alginate, povidone, dextran, polycaprolactone, chitosan, polylactic acid, glycolide-lactide copolymer, polyglycolide, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, stearic acid, carbomer, poloxamer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, and polyvinyl pyrrolidone; the molecular weight of the carrier material is 4000-600000; The surfactant includes at least one of stearic acid, fatty acid glyceride, sodium dodecylbenzene sulfonate, quaternary ammonium compound, fatty acid sorbitan, polysorbate, azolam, lecithin, amino acid type, and betaine type; The carrier material has a viscosity of 20-2000 mPa·s at 30° C. at a concentration of 0.5%; The solvent content in the drug coating is 2 wt%-5 wt%; The friction coefficient of the drug coating is below 0.

6.

2. The drug coating according to claim 1, characterized in that: Based on the total mass of the raw materials, it also includes less than 2 wt% of a humectant; The moisturizing agent includes at least one of glycerin, propylene glycol, butylene glycol, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, and sorbitol.

3. The drug coating according to claim 1, characterized in that: The invention comprises the following components based on the total weight of the raw materials: 1 wt%-19.9 wt% of a drug, 80 wt%-98 wt% of a carrier substance and 0.01 wt%-1 wt% of a surfactant.

4. A method for preparing the drug coating according to any one of claims 1 to 3, characterized in that: The following steps are involved: Step 1: Add the raw materials into a proper amount of solvent, control the temperature below 40°C to dissolve, mix evenly, and obtain a coating solution; Step 2: applying the coating solution to the surface of the medical device to be loaded with drugs, and drying to obtain a drug coating; In the step 1, the temperature during the mixing process is 35-65°C; In the step 2, the temperature during the coating process is 25-50° C.; the temperature during the drying process is 40-50° C., and the ambient humidity during the drying process is below 10% RH; The prepared drug coating has a solvent content of 2 wt%-5 wt%; The friction coefficient of the prepared drug coating is less than 0.6; Based on the total mass of the raw materials and the solvent, the amount of the solvent is 65wt%-90wt%; The viscosity of the coating solution prepared in step 1 is 500-5000 mPa·s at 30° C.

5. The method according to claim 4, characterized in that The solvent includes water and / or ethanol.

6. The method according to claim 4, characterized in that In step 2, the following steps are included: The coating solution is applied to the surface of the medical device to be loaded with drugs by spraying: the temperature of the coating solution is controlled to 28-45°C, the coating solution is stirred at the same time, and the coating time is controlled within 6 hours; the spraying parameters include: the spraying speed is 0.2-0.7 ml / min, the air inlet temperature is 40-50°C, and the air inlet speed is 1.5-2.0 m 3 / min.

7. The method according to claim 4, characterized in that In step 2, the following steps are included: The coating solution is applied to the surface of the medical device to be loaded with drugs by dipping: the temperature of the coating solution is controlled to be 28°C-35°C, and the coating time is within 12 hours; the part of the medical device to be loaded with drugs to be coated is immersed in the coating solution, the medical device to be loaded with drugs is taken out from the coating solution, the speed is increased to 0.1-4cm / s, and the medical device to be loaded with drugs is horizontally rotated at a speed of 10-20r / min, so that the coating solution is evenly dispersed on the surface of the medical device to be loaded with drugs as the temperature decreases and the solvent evaporates, thereby obtaining a drug coating.

8. The method according to any one of claims 4 to 6, characterized in that: The friction coefficient of the drug coating is 0.4-0.

6.

9. Use of the drug coating according to any one of claims 1 to 3 or the drug coating prepared by the method according to any one of claims 4 to 8 in preparing a drug-loaded medical device for biopsy or tumor ablation.

10. A drug-carrying medical device, characterized in that: The drug coating according to any one of claims 1 to 3 or the drug coating prepared by the method according to any one of claims 4 to 8 is applied to the surface of the drug-carrying medical device.

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