Drug-loaded skull nail

Abstract

The invention relates to the technical field of medical treatment, and particularly discloses a drug-loaded skull nail. The screw rod is provided with a front end, a rear end and an internal accommodating cavity; the nut is connected to one of the front end and the rear end of the screw rod; the sustained-release medicine is accommodated in the internal accommodating cavity; an opening connected with the outside is formed in the surface of the inner containing cavity. The bone nail can be slowly absorbed by a human body in an in-vivo microenvironment while ensuring that the whole bone nail has certain strength. Absorbable non-metallic material mixed medicine particles are adopted in the bone nail, and corresponding absorption time is designed according to different medicine characteristics, so that the medicine can be slowly released according to requirements.

Description

Technical Field

[0001] The present application relates to the field of medical technology, and in particular to a drug-loaded skull nail. Background Art

[0002] In the field of brain disease treatment, progress in the treatment of central nervous system (CNS) diseases has been hampered by the blood-brain barrier (BBB) ​​that restricts the entry of molecules into the brain. Many approaches to brain drug delivery that overcome the BBB have been explored, such as BBB permeability enhancement, transient BBB disruption, and direct surgical administration, but with limited success. Recent studies have shown that there are direct vascular channels between the skull bone marrow and the meninges, allowing the migration of bone marrow cells and lymphocytes. Related studies have proposed for the first time that intraosseous administration of drugs into the skull (intracranial [ICO]) as a new approach for brain drug delivery via a BBB bypass pathway. At the same time, the feasibility of this approach was finally tested through relevant simulation experiments on the mouse skull.

[0003] However, the current method of drug delivery through the skull bone marrow is not very mature. The existing skull bone marrow drug delivery technology still has the following problems: first, improper control of the traditional skull puncture method can easily cause brain tissue damage; second, the traditional drug delivery device cannot be left in the patient's body, and during the long-term drug delivery process, the patient has to repeatedly experience the pain of drug delivery. Summary of the invention

[0004] In order to solve the above problems, the present application provides a drug-loaded skull nail, which uses alloy metal that can be absorbed by the human body as the manufacturing material of the skull nail, while ensuring that the overall nail has a certain strength, it can be slowly absorbed by the human body in the microenvironment in the body without causing adverse effects such as human rejection reactions. Absorbable non-metallic materials are mixed with drug particles inside the nail, and the corresponding absorption time is designed according to different drug properties, so that the drug can be slowly released according to demand.

[0005] Additional features and advantages of the present application will be partially explained in the following description, and will be apparent to some extent from the description, or can be known by the practice of the present application. The purpose and other advantages of the present application will be realized and obtained by the elements and combinations particularly pointed out in the appended claims of the specification.

[0006] In order to obtain the above advantages, the present application provides a drug-loaded skull nail, comprising: a screw rod, provided with front and rear ends and an internal accommodating cavity; a nut, the nut being connected to one end of the front and rear ends of the screw rod; a sustained-release drug, contained in the internal accommodating cavity; wherein, a feature of the present application is that the surface of the internal accommodating cavity is provided with a plurality of openings connected to the outside, so that the sustained-release drug contained in the internal accommodating cavity can be released into the human body medium through the openings after entering the human body and dissolving. At the same time, the size of the opening needs to be compatible with the shape and size of the sustained-release drug, so as to achieve a sustained and sufficient sustained-release drug delivery effect of the drug-loaded skull nail in the body. Preferably, the opening is a circle with a radius of 1.5mm to 1.8mm, and the sustained-release drug is a spherical particle with a radius of 1.6mm to 2.0mm. Within this value range, the drug-loaded skull nail can meet the actual required drug sustained-release rate.

[0007] In order to allow the skull nail to pass through the skull and the blood-brain barrier and be embedded in the skull for drug delivery, one feature of the present application is that the diameter of the screw gradually decreases in the extension direction from the rear end to the front end, and the front end of the screw can be at a cone angle of 15-80 degrees, which can penetrate the skull without causing damage to the dura mater. At the same time, the surface of the screw is formed with threads, which makes it easier for the skull nail to pass through the skull and fix its position in the skull to prevent detachment and damage.

[0008] In order to allow the skull nail to be more conveniently embedded in the skull and to more easily adjust its depth in the skull, a feature of the present application is that the nut is connected to the rear end of the screw rod, and the user can drive the screw rod to rotate into the skull by rotating the nut.

[0009] In order to prevent the drug from dissolving immediately after entering the human body environment, thereby achieving the effect of sustained release of the drug, another feature of the present application is that the sustained release drug is made by coating the surface of the drug with a coating material, preferably, the coating material is polylactic acid. Polylactic acid is relatively stable at room temperature, but it is easy to quickly degrade into CO2 and water in a slightly higher temperature environment, acid-base environment, and microbial environment. Therefore, after the drug enters the human body environment with the skull nail, the polylactic acid coated on its surface will slowly decompose in the human body environment. When the decomposition reaches a certain degree, the body fluid will penetrate the polylactic acid layer coated on the surface of the drug, thereby slowly decomposing the drug and then releasing it into the human body environment with the body fluid.

[0010] In order to prevent the drug from leaking out from the opening on the surface of the screw before entering the human body environment with the skull nail, a feature of the present application is to set the size of the opening to be smaller than the cross-sectional size of the sustained-release drug, so that the sustained-release drug cannot pass through the opening before the drug-loaded skull nail enters the human body.

[0011] In order to avoid the traditional skull drug delivery method being unable to remain in the patient's body, and causing the patient to experience repeated pain during the long-term drug delivery process, another feature of the present application is that the screw and nut are both metals that can be absorbed by the human body. Preferably, the screw and nut are one or more of magnesium alloy, zinc alloy or iron alloy, which are metals that can be absorbed by the human body and have good biocompatibility. Magnesium, zinc and iron are all essential constant elements for the human body, so safety can be guaranteed, and the excess can also be excreted from the body through urine and other channels. At the same time, magnesium alloy, zinc alloy or iron alloy have a certain mechanical strength, which is enough for the skull nail to pass through the skull, and it is not easy to deform under stress in the skull, causing intracranial injury. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the description of the embodiments of the present application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0013] Figure 1 This is a schematic diagram of the overall appearance of a skull pin according to an embodiment of the present application;

[0014] Figure 2 is a cross-sectional schematic diagram of a sustained-release drug in one embodiment of the present application;

[0015] Figure 3 is a schematic cross-sectional view of a skull pin according to an embodiment of the present application;

[0016] Figure 4 It is a comparison chart of the sustained release curves of the drugs in Example 1 and Example 2 of the present application;

[0017] Figure 5 It is a comparison chart of the sustained release curves of the drugs in Examples 2 to 6 of the present application;

[0018] Figure 6 It is a comparison diagram of the drug sustained release curves of Example 1 and Comparative Example 1 of the present application;

[0019] Figure 7 It is a comparison diagram of the sustained release curves of the drugs in Example 1 and Comparative Example 2 of the present application;

[0020] Figure 8 It is a comparison chart of the drug sustained release curves of Example 1 and Comparative Example 3 of the present application.

[0021] Description of Reference Numerals

[0022] 1-drug-loaded skull nail, 2-nut, 3-screw, 4-opening, 5-thread, 6-nut groove, 7-rear end of screw, 8-front end of screw, 9-internal accommodating cavity. DETAILED DESCRIPTION

[0023] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present application.

[0024] In the description of the embodiments of the present application, it should be noted that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inside", "outside", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product is usually placed when in use, which is only for the convenience of describing the embodiments of the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the embodiments of the present application. In addition, the terms "first", "second", "third", etc. are only used to distinguish the description and cannot be understood as indicating or implying relative importance. In the description of the embodiments of the present application, unless otherwise specified, the meaning of "multiple" is two or more.

[0025] In the description of the embodiments of the present application, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "setting" and "connection" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection. For ordinary technicians in this field, the specific meanings of the above terms in the embodiments of the present application can be understood according to specific circumstances.

[0026] In the embodiments of the present application, unless otherwise clearly specified and limited, the first feature being "above" or "below" the second feature may include the first and second features being in direct contact, or may include the first and second features not being in direct contact but being in contact through another feature between them. Moreover, the first feature being "above", "above" and "above" the second feature includes the first feature being directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. The first feature being "below", "below" and "below" the second feature includes the first feature being directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0027] Likewise, it is to be understood that the phrases and terms used herein are for descriptive purposes and should not be considered restrictive. The use of "include," "comprise," or "have" and variations thereof herein is intended to be open to include the items listed thereafter and their equivalents and additional items.

[0028] In the description of the embodiments of the present application, "distal" and "proximal" are used as directional words, which are commonly used terms in the field of interventional medical devices, where "distal" refers to the end away from the operator during the operation, and "proximal" refers to the end close to the operator during the operation.

[0029] The drug-loaded skull nail 1 according to an embodiment of the present application is described in detail below.

[0030] Figure 1 This is a schematic diagram of the overall appearance of a drug-loaded skull nail according to an embodiment disclosed in the present application. Figure 3 This is a schematic cross-sectional view of a drug-loaded skull nail in a vertical direction according to an embodiment disclosed in the present application. Figure 1 and Figure 3 According to a drug-loaded skull nail 1 disclosed in the present application, it includes a screw rod 3, a nut 2 and a sustained-release drug 11. A hollow internal accommodating chamber 9 is provided inside the screw rod 3 for accommodating the sustained-release drug 11 therein. The drug-loaded skull nail 1 enters the human body environment together with the drug-loaded skull nail 1. It should be noted that an opening 4 is provided on the outer surface of the screw rod 3. The opening 4 can realize the connection between the internal accommodating chamber 9 of the screw rod 3 and the external environment of the screw rod, so that after the drug-loaded skull nail 1 enters the human body environment, the sustained-release drug 11 in the internal accommodating chamber 9 of the screw rod 3 can contact the body fluid through the opening 4, thereby being dissolved and released.

[0031] According to the embodiments disclosed in the present application, the screw rod 3 includes front and rear ends. In some embodiments, the diameter of the screw rod 3 gradually decreases in the extension direction from the rear end 7 to the front end 8. It is understandable that the diameter of the screw rod 3 in the extension direction from the rear end 7 to the front end 8 can be kept consistent or slightly increased in some parts without affecting the embedding of the drug-loaded skull nail into the skull. Preferably, the front end 8 of the screw rod 3 has a cone angle of 15-80 degrees, and more preferably, the front end has a cone angle of 20-45 degrees, so that the drug-loaded skull nail 1 can be better embedded in the skull without causing skull damage.

[0032] Continue to see Figure 1According to the embodiments disclosed in the present application, the nut 2 is connected to the rear end 7 of the screw 3. In some embodiments, the lower surface of the nut 2 in a positive posture is fixedly connected to the outer surface of the rear end 7 of the screw 3. It is understandable that the nut 2 can be connected to the rear end 7 of the screw 3 by glue, electric welding or integral molding. It should be noted that in some embodiments, a nut groove 6 is provided on the upper surface of the nut 2, and the groove 6 can be set as a cross-shaped groove or a straight groove or any other shape that can be used as a nut groove. The user can use a tool such as a screwdriver to twist the nut 2 in a clockwise or counterclockwise direction to drive the screw 3 to rotate into the skull.

[0033] According to the embodiments disclosed in the present application, a thread 5 is formed on the surface of the screw, and the thread 5 can be a triangular thread, a trapezoidal thread, a circular thread, etc. The cross-sectional shape of the triangular thread is a triangle, which has the advantages of low manufacturing cost and easy processing, but the disadvantages are low pressure bearing capacity, easy to break, and not suitable for being subjected to large pressure. The cross-sectional shape of the trapezoidal thread is a trapezoid, which has the advantages of high bearing capacity and suitable for bearing large pressure, but the disadvantages are high manufacturing cost and high processing difficulty. The cross-sectional shape of the circular thread is a circle, which has the advantages of low cost and easy processing, but the disadvantage is that it is not suitable for bearing large pressure. It can be understood that the shape of the thread 5 used in the present application is not limited to this, and can also be other shapes.

[0034] See also Figure 2 According to the embodiments disclosed in the present application, the sustained-release drug 11 is made by wrapping the coating material on the surface of the drug 13. In some embodiments, the sustained-release drug 11 also achieves sustained-release efficacy by other means. For example, in some embodiments, the sustained-release drug is a hydrophilic gel skeleton tablet, which is a tablet made by compression molding of a drug and one or more inert fixed skeleton materials, and the main skeleton material of the hydrophilic skeleton tablet is one or more of HPMC, hydroxyethyl cellulose, sodium CMC, and sodium alginate. Preferably, in the sustained-release drug 11, the hydrophilic skeleton tablet material accounts for 20% to 40% of the total content. In some embodiments, the preparation method of the sustained-release drug 11 is: mix the drug and sodium hydroxymethyl cellulose evenly, then granulate and dry with 95% ethanol, then add HPMC and microcrystalline cellulose, mix evenly, add magnesium stearate to the whole granules, mix well and press tablets.

[0035] According to the embodiments disclosed in the present application, the coating material coated on the surface of the drug 13 is polylactic acid, which is relatively stable at room temperature, but is easily and rapidly degraded into CO2 and water in a slightly higher temperature environment, acid-base environment, and microbial environment. Therefore, after the drug enters the human body environment with the skull nail, the polylactic acid coated on its surface will slowly decompose in the human body environment. When the decomposition reaches a certain degree, the body fluid will penetrate the polylactic acid layer coated on the surface of the drug, thereby slowly decomposing the drug and then releasing it into the human body environment with the body fluid. It can be understood that in addition to polylactic acid, the coating material according to the embodiments disclosed in the present application can also be one or more of cellulose acetate, ethyl cellulose, and methacrylic acid copolymer.

[0036] Continue to refer to Figure 2 In some embodiments, the coating material includes components such as a plasticizer, a release rate regulator (porogen), an anti-adherent, a sunscreen, and a solvent or medium in addition to polylactic acid. According to the embodiments disclosed in the present application, the plasticizer is polyethylene glycol 400 or triethyl citrate, the sunscreen is iron oxide, and the porogen is one or more of cellulose derivatives, PVPP, carbomer, or talc.

[0037] Continue to refer to Figure 2 , the size of the opening 4 is smaller than the cross-sectional size of the sustained-release drug 11, so that before the drug-loaded skull nail 1 enters the human body, the sustained-release drug cannot pass through the opening 4. It can be understood that the area of ​​the opening 4 can be larger than the cross-sectional area of ​​the sustained-release drug 11, but the shape of the opening 4 needs to be designed as a shape that the sustained-release drug 11 cannot pass through. For example, the cross-sectional size of the opening 4 is set to be a rectangle with a length much larger than the width, and its overall area is larger than the sustained-release drug 11, but it still cannot pass through the opening 4 due to its narrow width.

[0038] Reference Figure 1 According to the embodiments disclosed in the present application, the screw and nut are both metals that can be absorbed by the human body. It should be noted that the metal that can be absorbed by the human body is a metal that is easily corroded and degraded in the human body environment. Preferably, the screw and nut are both one or more of magnesium alloy, zinc alloy or iron alloy.

[0039] The present invention will be further explained below by way of examples.

[0040] Example 1

[0041] Embodiment 1 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.5 mm. The internal accommodating cavity also contains sustained-release drugs, which include a neuroprotectant NA-1 and a coating material polylactic acid located on the outer surface. The sustained-release drugs are single spherical particles with a radius of 1.8 mm.

[0042] Example 2

[0043] Embodiment 2 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.5 mm. The internal accommodating cavity also contains sustained-release drugs, and the sustained-release drugs include anti-ischemic stroke drug Y-3 and polylactic acid, a coating material located on the outer surface. The sustained-release drugs are single spherical particles with a radius of 1.8 mm.

[0044] Example 3

[0045] Embodiment 3 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.2 mm. The internal accommodating cavity also contains sustained-release drugs, and the sustained-release drugs include anti-ischemic stroke drug Y-3 and polylactic acid, a coating material located on the outer surface. The sustained-release drugs are single spherical particles with a radius of 1.8 mm.

[0046] Example 4

[0047] Embodiment 4 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.5 mm. The internal accommodating cavity also contains sustained-release drugs, and the sustained-release drugs include anti-ischemic stroke drug Y-3 and polylactic acid, a coating material located on the outer surface. The sustained-release drugs are single spherical particles with a radius of 1.6 mm.

[0048] Example 5

[0049] Embodiment 4 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.2 mm. The internal accommodating cavity also contains sustained-release drugs, and the sustained-release drugs include anti-ischemic stroke drug Y-3 and polylactic acid, a coating material located on the outer surface. The sustained-release drugs are single spherical particles with a radius of 1.6 mm.

[0050] Example 6

[0051] Embodiment 6 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.8 mm. The internal accommodating cavity also contains sustained-release drugs, and the sustained-release drugs include anti-ischemic stroke drug Y-3 and polylactic acid, a coating material located on the outer surface. The sustained-release drugs are single spherical particles with a radius of 2.0 mm.

[0052] Comparative Example 1

[0053] Comparative Example 1 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.5 mm. The internal accommodating cavity also contains a neuroprotectant NA-1, and the sustained-release drug is a single spherical particle with a radius of 1.8 mm.

[0054] Comparative Example 2

[0055] Comparative Example 2 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 0.8 mm. The internal accommodating cavity also contains sustained-release drugs, which include a neuroprotectant NA-1 and a coating material polylactic acid located on the outer surface. The sustained-release drug is a single spherical particle with a radius of 2.4 mm.

[0056] Comparative Example 3

[0057] Comparative Example 3 of the present invention provides a drug-loaded skull nail, which is made of magnesium alloy and is provided with an internal accommodating cavity for drug loading. The surface of the internal accommodating cavity is provided with 8 openings connected to the outside, and the openings are circular with a radius of 1.5 mm. The internal accommodating cavity also contains sustained-release drugs, which include a neuroprotectant NA-1 and a coating material polylactic acid located on the outer surface. The sustained-release drug is a single spherical particle with a radius of 0.8 mm.

[0058] The parameters of the above embodiments and comparative examples are shown in Table 1.

[0059] Table 1

[0060]

[0061] The structural dimensions of the drug-loaded skull nail involved in the present invention are adapted to the design of the human skull structure. It is technically difficult to test the sustained release effect in small animals, and it is difficult to ensure the consistency of the data. Therefore, an in vitro sustained release experiment is designed to quantitatively test the sustained release characteristics of the absorbable drug-loaded skull nail.

[0062] Test on the cumulative drug release rate of drug-loaded skull nails:

[0063] Accurately weigh the weight of the drug-loaded skull nails of Examples 1-6 and Comparative Examples 1-3 to calculate the drug loading of each skull nail, and then completely immerse each skull nail in a test tube containing 10 mL PBS, and shake in a constant temperature water bath at 37° C. and 100 r / min. At 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, and 5 weeks, take out all the solutions with a pipette, bottle them for testing, and replace them with fresh 10 mL PBS to continue releasing the drugs in the dark. Finally, measure the drug concentration at each time point by a high-efficiency chromatography column method, and calculate the cumulative drug release percentage of the skull nail according to the following formula.

[0064]

[0065] Where: Vi—volume of each sampling, mL;

[0066] Ci—concentration of the drug sampled at the i-th time in the medium, mg / mL;

[0067] M—Total dosage of skull nail, mg.

[0068] Chromatographic conditions: Column: AcquityUPLC BEHC18 column (2.1 mm × 100 mm, 1.7 μm; Waters, USA). Mobile phase A is 20 mmol / L Na2HPO4 buffer solution, adjusted to pH 4.5 with H3PO4; mobile phase B is methanol; isocratic A:B = 35:65; column temperature is 25°C. Flow rate is 0.21 mL / min; injection volume: 1.0 μL. NA-1 standard curve: y = 2310x-13400 (R2 = 0.9997); Y-3 standard curve: y = 3340x-4220 (R2 = 0.9995); where x is the drug concentration and y is the area of ​​the drug peak.

[0069] The cumulative drug release rate (%) test results of the drug-loaded skull nails of Examples 1-6 and Comparative Examples 1-3 are shown in Table 2, and the drug sustained release curves are shown in Appendix Figure 4-8 .

[0070] Table 2

[0071] 1d 2d 3d 4d 5d 6d 7d 2w 3w 4w 5w Example 1 12.75 27.44 35.42 41.28 48.58 57.27 71.68 77.56 84.42 91.41 98.28 Example 2 10.31 20.33 28.41 34.44 42.14 49 58.5 71.12 81.2 88.34 98.13 Example 3 10.75 21.12 25.86 31.36 42.23 47.98 55.62 70.44 80.58 87.69 97.95 Example 4 10.52 20.69 24.92 30.84 41.92 48.63 57.42 71.13 82.66 88.13 98.75 Example 5 10.23 21.72 26.22 31.91 42.1 45.68 56.35 72.28 81.53 87.37 98.95 Example 6 11.25 22.63 27.25 32.12 42.25 48.42 57.62 71.73 82.52 89.21 98.86 Comparative Example 1 21.67 35.43 52.15 78.12 95.43 98.72 99.43 99.58 99.72 99.82 99.84 Comparative Example 2 8.52 10.21 12.43 13.52 15.33 17.42 21.67 32.43 40.42 45.15 49.87 Comparative Example 3 32.52 47.33 62.41 72.22 80.16 88.37 93.69 98.15 99.91 99.94 99.97

[0072] By comparing the cumulative drug release rate results and drug sustained release curves of Example 1 and Example 2, it can be seen that although different types of sustained-release drugs have different release rates at corresponding time points, the overall trends of the drug sustained-release curves are the same (see Appendix Figure 4 ).

[0073] By comparing the cumulative drug release rate results and drug sustained release curves of Examples 2 to 6, it can be seen that the opening radius is between 1.2 mm and 1.8 mm, and the sustained release drug radius is between 1.6 mm and 2.0 mm. The sustained release rate of the drug is not much different and the drug sustained release curve is very good (see Appendix Figure 5 ), to meet the needs of continuous and sufficient drug delivery.

[0074] By comparing the cumulative drug release rate results and drug sustained release curves of Example 1 and Comparative Example 1, it can be seen that the drug in Comparative Example 1 is basically released in a very short time (see Figure 6 ), indicating that it is difficult to achieve a good sustained-release effect without coating.

[0075] By comparing the cumulative drug release rate results and drug sustained release curves of Example 1 and Comparative Example 2, it can be seen that the drug sustained release rate of Comparative Example 2 is very slow compared with that of Example 1, and the drug release rate has not exceeded 50% after 5 weeks (see Figure 7 ), and the appropriate dosage cannot be achieved at the corresponding time point. This indicates that the radius of the opening is too small, and the radius of the sustained-release drug will cause the drug release rate to be too slow, and the basic dosage cannot be achieved.

[0076] By comparing the cumulative drug release rate results and drug sustained release curves of Example 1 and Comparative Example 3, it can be seen that the drug sustained release rate of Comparative Example 3 is too fast compared with that of Example 1 (see Figure 8 ), the drug sustained release effect cannot be achieved, indicating that the radius of the opening needs to be smaller than the radius of the sustained-release drug in order to achieve the sustained-release effect.

[0077] The embodiments described above are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application, and should all be included in the protection scope of the present application.

Claims

1. A drug-loaded skull nail, characterized in that: include: The screw rod is provided with front and rear ends and an internal accommodating cavity; A nut connected to the rear end of the screw; A sustained-release drug contained in the internal containing cavity; Wherein, the surface of the internal accommodating cavity is provided with a plurality of openings connected to the outside.

2. The drug-loaded skull nail according to claim 1, characterized in that: The opening is circular.

3. The drug-loaded skull nail according to claim 2, characterized in that: The radius of the opening ranges from 1.5 mm to 1.8 mm.

4. The drug-loaded skull nail according to claim 1, characterized in that: The surface of the screw rod is formed with threads.

5. The drug-loaded skull nail according to claim 1, characterized in that: The sustained-release drug is prepared by coating the drug surface with a coating material.

6. The drug-loaded skull nail according to claim 5, characterized in that: The coating material is polylactic acid.

7. The drug-loaded skull nail according to any one of claims 1 to 6, characterized in that: Before the drug-loaded skull nail enters the human body, the sustained-release drug cannot pass through the opening.

8. The drug-loaded skull nail according to claim 7, characterized in that: The sustained-release drug is in the form of spherical particles, and the radius of the sustained-release drug ranges from 1.6 mm to 2.0 mm.

9. The drug-loaded skull nail according to claim 1, characterized in that: The screw rod and the nut are both metals that can be absorbed by the human body.

10. The drug-loaded skull nail according to claim 9, characterized in that: The screw and nut are made of one or more of magnesium alloy, zinc alloy or iron alloy.

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