Mesoporous silicon drug carrier retained in blood vessel for long time and transmission mode thereof based on liquid perfusion balloon

Abstract

The invention discloses a preparation method of a meso-porous silicon drug carrier retained in blood vessels for a long time. The preparation method comprises the following steps: reacting meso-porous silicon dioxide with a functionalized silane coupling agent to obtain surface-functionalized meso-porous silicon dioxide, and reacting the surface-functionalized meso-porous silicon dioxide with phenylboronic acid molecules to obtain the meso-porous silicon drug carrier. The meso-porous silicon drug carrier can load a drug to form a drug compound, the drug compound can be uniformly dispersed in a dispersant to form a drug compound dispersion liquid, and the drug compound dispersion liquid can be used for a liquid perfusion balloon. The liquid perfusion balloon can be used for treating vascular diseases, the liquid perfusion balloon can be conveyed to a diseased region in a blood vessel, the interior of the liquid perfusion balloon can be inflated, the medicine compound dispersion liquid in the liquid perfusion balloon can be extruded into the blood vessel, and the medicine compound can be preserved in the blood vessel for a long time.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a mesoporous silica drug carrier that can be stored in blood vessels for a long time and its delivery method based on a liquid perfusion balloon. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Cardiovascular disease is currently the leading cause of illness and death worldwide, and its incidence continues to grow rapidly, posing a serious threat to public health. Percutaneous coronary angioplasty (PTCA) is a crucial treatment for cardiovascular disease. PTCA has evolved through several stages, including bare-metal balloons, bare-metal stents, and drug-eluting stents. Drug-eluting stents are currently the "gold standard" and have achieved great success. However, due to long-term implantation and incompatibility with vascular biomechanics, as well as side effects such as late-stage thrombosis, its therapeutic efficacy remains limited.

[0004] Drug-coated balloons (DCBs) were developed to address this issue, as they can efficiently release drugs to inhibit endometrial hyperplasia without leaving permanent devices in the patient's body, demonstrating good therapeutic potential.

[0005] Existing DCBs have certain shortcomings, such as: (1) Drug crystals are prone to detachment during the delivery process, resulting in low drug delivery efficiency; (2) The drug enters the blood vessels by puncture, which causes greater damage to the blood vessel wall. At the same time, the long-term contact between the vascular endothelium and the drug leads to delayed repair and increases the risk of late thrombosis. (3) The drug dosage is uncontrollable.

[0006] To address these issues, liquid-perfusion balloons have been developed. The drug solution enters the inner tube of the balloon and is released through the microporous structure on the balloon surface, offering advantages such as reduced drug loss during delivery, no particle shedding, and controllable drug dosage. For example, patent specification CN104436421A discloses a perfusionable drug balloon, comprising a balloon body with a cylindrical conduit in the middle and elastic balloons at both ends. The diameter of the balloon portions is larger than the cylindrical ends, forming protrusions. One end of the balloon body is connected to a drug source via a conduit. The outer wall of the conduit has micropores arranged in several layers along the axial direction, with each layer of micropores evenly distributed around the axis of the balloon body. The outflow of drug solution from all the micropores on the balloon body is less than the inflow of drug solution through the connecting tube.

[0007] However, due to the loose structure of the vascular membrane and the continuous fluid exchange with the lymphatic system, drugs entering the bloodstream in liquid form typically suffer from short retention times and are easily degraded and cleared. Therefore, drugs cannot maintain effective concentrations in tissues for extended periods, limiting therapeutic efficacy. Summary of the Invention

[0008] To address the aforementioned technical problems and shortcomings in the field, this invention provides a mesoporous silica drug carrier for long-term intravascular retention and its delivery method based on a liquid perfusion balloon, thereby solving the problems of current liquid perfusion balloons' inability to achieve drug retention and long-term therapeutic effects.

[0009] The specific technical solution is as follows: In a first aspect, the present invention provides a method for preparing a mesoporous silica drug carrier that can be stored in blood vessels for a long time, comprising: reacting mesoporous silica with a functionalized silane coupling agent to obtain surface-functionalized mesoporous silica, and reacting the surface-functionalized mesoporous silica with phenylboronic acid molecules to obtain the mesoporous silica drug carrier.

[0010] The reaction between the mesoporous silica and the functionalized silane coupling agent involves the functionalized silane coupling agent undergoing hydrolysis and / or alcoholysis, followed by condensation with hydroxyl groups on the surface of the mesoporous silica, thereby grafting onto the surface of the mesoporous silica to form surface-functionalized mesoporous silica.

[0011] In some embodiments, the mesoporous silica reacts with the functionalized silane coupling agent as follows: the pH of the reaction system is 4–6.5 (e.g., 6), the reaction temperature is room temperature to 60°C, the reaction time is 2–12 h, the mass ratio of mesoporous silica to functionalized silane coupling agent is 1:0.1–1 (e.g., 1:0.3, 1:0.5, 1:0.7, etc.), and the reaction solvent includes water and / or ethanol. The pH of the reaction system can be adjusted using hydrochloric acid or the like.

[0012] The surface-functionalized mesoporous silica reacts with phenylboronic acid molecules in at least one of the following: aldehyde reaction with amino group to form Schiff base, ring-opening reaction of epoxy group with amino group, Michael addition reaction of carbon-carbon double bond with amino and / or mercapto group, condensation reaction of carboxyl group with amino group, and ring-opening reaction of epoxy group with carboxyl group.

[0013] In some embodiments, the surface-functionalized mesoporous silica reacts with phenylboronic acid molecules: the reaction system pH is 4-10 (e.g., 5.5, 6.0, 9.0, etc.), the reaction temperature is room temperature to 60°C, the reaction time is 0.5-12 h, the mass ratio of surface-functionalized mesoporous silica to phenylboronic acid molecules is 1:0.1-0.5 (e.g., 1:0.3, 1:0.4, etc.), and the reaction solvent includes water and / or methanol. The pH of the reaction system can be adjusted using hydrochloric acid, sodium hydroxide, etc.

[0014] The functionalized silane coupling agent may include at least one of 3-aminopropyltriethoxysilane (KH550), glycidyl etheroxypropyltrimethoxysilane (KH560), methacryloyloxypropyltrimethoxysilane (KH-570), and 3-mercaptopropyltrimethoxysilane (KH-590).

[0015] The phenylboronic acid molecules may include at least one of 4-formylphenylboronic acid, 3-formylphenylboronic acid, 2-formylphenylboronic acid, 4-carboxyphenylboronic acid, 3-carboxyphenylboronic acid, 2-carboxyphenylboronic acid, 4-aminophenylboronic acid, 3-aminophenylboronic acid, 2-aminophenylboronic acid, 4-allylphenylboronic acid, 3-allylphenylboronic acid, and 2-allylphenylboronic acid.

[0016] The mesoporous silica used in this invention can be synthesized according to existing technology or obtained through commercial means.

[0017] In some preferred embodiments, the mesoporous silica has a particle size of 20 to 1000 nm, such as 200 nm.

[0018] Secondly, the present invention provides a mesoporous silica drug carrier prepared by the preparation method described in the first aspect.

[0019] Thirdly, the present invention provides the application of the mesoporous silica drug carrier described in the second aspect for loading drugs. The drugs include, but are not limited to, at least one of rapamycin, octyl 4-itaconate, paclitaxel, indomethacin, colchicine, quercetin, dexamethasone, aspirin, 5-fluorouracil, antibody drugs, DNA / RNA drugs, and inhibitors.

[0020] Fourthly, the present invention provides a drug complex comprising the mesoporous silica drug carrier described in the second aspect and a drug loaded on the mesoporous silica drug carrier. The drug loaded on the mesoporous silica drug carrier includes, but is not limited to, at least one of rapamycin, octyl 4-itaconate, paclitaxel, indomethacin, colchicine, quercetin, dexamethasone, aspirin, 5-fluorouracil, antibody drugs, DNA / RNA drugs, and inhibitors.

[0021] Fifthly, the present invention provides a method for preparing the drug complex described in the fourth aspect, comprising: mixing a drug with the mesoporous silica drug carrier in a solvent (the solvent may specifically be water, ethanol, etc.), and incubating for a period of time (e.g., 24 h) to obtain the drug complex. The method for preparing the drug complex may further include separation operations such as centrifugation after incubation. Further, the centrifugation speed is 10000~15000 rpm, for example, 12000 rpm. The mass ratio of the drug to the mesoporous silica drug carrier can be 0.1~5:1, further 0.5~2:1, for example, 1:1.

[0022] In a sixth aspect, the present invention provides a drug complex dispersion comprising a dispersant and a drug complex as described in the fourth aspect, uniformly dispersed in the dispersant. The dispersant may include water, etc. In the drug complex dispersion, the mass concentration of the drug complex may be 0.1 to 1 mg / mL, for example, 0.5 mg / L, etc.

[0023] In a seventh aspect, the present invention provides a method for preparing the drug complex dispersion described in the sixth aspect, comprising: uniformly dispersing the drug complex in a dispersant to obtain the drug complex dispersion.

[0024] Eighthly, the present invention provides the application of the drug complex described in the fourth aspect or the drug complex dispersion described in the sixth aspect in a liquid perfusion balloon. The liquid perfusion balloon may be a single-layer balloon, a multi-layer balloon (e.g., a double-layer balloon), etc.

[0025] The liquid perfusion balloon can be used to inject the drug complex dispersion.

[0026] The liquid perfusion balloon can be used for the treatment of vascular diseases. Specifically, the liquid perfusion balloon can be delivered to the lesion site in the blood vessel. The interior of the liquid perfusion balloon can be inflated to squeeze the drug complex dispersion into the blood vessel. The drug complex can remain in the blood vessel for a long time.

[0027] In some applications, the liquid-infused balloon is a single-layer balloon.

[0028] In some applications, the liquid perfusion balloon has a two-layer structure with an inner and an outer layer, and a gap between the inner and outer layers. The drug complex dispersion is filled in the gap, and the inner layer of the liquid perfusion balloon can be inflated to expand the liquid perfusion balloon and squeeze out the drug complex dispersion.

[0029] The outer surface of the liquid perfusion balloon may be provided with micropores, permeation pores, etc., so that the drug complex dispersion can flow out and permeate.

[0030] Ninthly, the present invention provides a liquid perfusion balloon containing the drug complex dispersion described in the sixth aspect. The drug complex dispersion can be pre-infused into the liquid perfusion balloon, or it can be infused into the liquid perfusion balloon during its use in a blood vessel, or a combination of both methods.

[0031] The liquid perfusion balloon can be used to inject the drug complex dispersion.

[0032] In some embodiments, the liquid-infused balloon is a single-layer balloon.

[0033] In some embodiments, the liquid perfusion balloon has a two-layer structure of an inner layer and an outer layer, with a gap between the inner and outer layers. The drug complex dispersion is filled in the gap, and the inner layer of the liquid perfusion balloon can be inflated to expand the liquid perfusion balloon and squeeze out the drug complex dispersion.

[0034] The outer surface of the liquid perfusion balloon can be provided with micropores, permeation pores, etc., to allow the drug complex dispersion to flow out and permeate.

[0035] A delivery method based on the liquid-infused balloon described in the ninth aspect includes: Delivering a fluid-perfusion balloon to the lesion site within the blood vessel; Inflation causes the internal balloon to expand, allowing it to conform to the blood vessel wall; The drug complex dispersion is infused into the cavity between the two balloon layers. Pressure is applied to force the liquid out of the micropores and / or permeable pores on the surface of the outer balloon and directly into the blood vessel wall.

[0036] The mechanism by which the mesoporous silica drug carrier and drug complex of the present invention can remain in blood vessels for a long time is as follows: The media of blood vessels contains a large amount of extracellular matrix, which contains a large amount of polysaccharides and proteoglycans, including heparin, hyaluronic acid, chondroitin sulfate, heparan sulfate, etc. The ortho-dihydroxy structure in the polysaccharide structure can spontaneously react with the phenylboronic acid structure to form a chemical bond, thereby fixing the mesoporous silica drug carrier and drug complex inside the extracellular matrix and thus avoiding being cleared.

[0037] Compared with the prior art, the beneficial effects of this invention are as follows: 1) After entering the tissue, the mesoporous silica drug carrier can react with the extracellular matrix, thereby achieving long-term retention in blood vessels and avoiding drug clearance by lymphatic transport.

[0038] 2) Bioactive drugs are rapidly metabolized and enzymatically degraded in tissues. By loading bioactive drugs onto mesoporous silica, their bioactivity can be protected for a long time.

[0039] 3) Mesoporous silica drug carriers can also achieve long-term sustained release of drugs, thereby ensuring that the drugs maintain an effective concentration in the blood vessels for a long time and achieve long-term treatment. Attached Figure Description

[0040] Figure 1 This is a transmission electron microscope (TEM) image of drug-loaded mesoporous silicon from Example 1.

[0041] Figure 2 This is a distribution diagram of the mesoporous silica drug carrier loaded with fluorescein isothiocyanate (FITC) modified bovine serum albumin in Example 1 after delivery via a liquid perfusion balloon in the blood vessel wall.

[0042] Figure 3 The images show the intravascular drug retention in Example 1 and Comparative Examples 1 and 2 after 3 days, 1 week, and 4 weeks of delivery via a liquid-perfused balloon to drug-loaded mesoporous silica. Detailed Implementation

[0043] Terminology explanation: "In the blood vessel" refers to the blood vessel wall, especially the intima and media layers, which are 10 to 500 micrometers thick.

[0044] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0045] Unless otherwise specified, the operating methods in the following examples are generally performed under conventional conditions or as recommended by the manufacturer.

[0046] In the following examples, a liquid perfusion balloon with an inner and outer layer structure is used. A gap is left between the inner and outer layers to allow for the perfusion and filling of the drug complex dispersion. The outer layer surface has micropores. When in use, the inner layer of the liquid perfusion balloon can be inflated to expand the liquid perfusion balloon and squeeze out the perfused drug complex dispersion.

[0047] The migration and action process of the drug complex dispersion of the present invention are illustrated as follows: squeezed to the outside of the balloon → released to the vascular wall → rapidly and efficiently penetrated into the vascular wall tissue (especially at the location of plaque) for a long time → acted on the target site.

[0048] Example 1: In an ethanol / water mixture with a volume ratio of 80 / 20, 1 g of mesoporous silica (particle size 200 nm) was mixed with 0.5 g of 3-aminopropyltriethoxysilane and reacted at room temperature for 12 h. The reaction pH was 6.0 (adjusted with hydrochloric acid) to obtain amino-modified mesoporous silica.

[0049] In a methanol / water mixture with a volume ratio of 50 / 50, 1 g of amino-modified mesoporous silica was mixed with 0.3 g of 4-formylphenylboronic acid and reacted at room temperature for 12 h. The reaction pH was 9.0 (adjusted with sodium hydroxide) to obtain a mesoporous silica drug carrier.

[0050] 1 mL of 10 mg / mL mesoporous silica drug carrier aqueous dispersion was mixed with 1 mL of 10 mg / mL tocilizumab aqueous solution, incubated for 24 h, and then centrifuged at 12000 rpm to obtain drug-loaded mesoporous silica. The remaining concentration of tocilizumab in the centrifuged supernatant was detected by an ELISA kit, and the tocilizumab loading in the mesoporous silica drug carrier was calculated to be 0.62 ± 0.06 mg / mg.

[0051] Drug-loaded mesoporous silica was uniformly dispersed in water to obtain a drug-loaded mesoporous silica solution with a concentration of 0.5 mg / mL.

[0052] A liquid-perfusion balloon is delivered into the blood vessel and pressurized to 8 atm to ensure it adheres tightly to the vessel wall. Next, a drug-loaded mesoporous silica solution is infused into the space between the two balloon layers of the liquid-perfusion balloon, and the pressure is increased to 10 atm. The drug is then expelled from the micropores on the surface of the liquid-perfusion balloon into the blood vessel, delivering a volume of 100 μL.

[0053] The structure of drug-loaded mesoporous silicon was analyzed using transmission electron microscopy, such as... Figure 1 As shown, the particle size of the drug-loaded mesoporous silica is 216±22 nm. Through theoretical calculations of the injection volume, the tocilizumab delivery rate on the balloon can reach approximately 6 μg / mm². 2 This is higher than the drug loading capacity of existing drug-eluting balloons (2~3 μg / mm). 2 ).

[0054] After the blood vessels were removed from the balloon and homogenized, the drug delivery was tested using an ELISA kit. The drug delivery efficiency was found to be as high as 80%, which is much higher than the 10% of traditional drug-coated balloons.

[0055] Mesoporous silica drug carriers loaded with FITC-modified bovine serum albumin were used as a model for the above-mentioned balloon delivery, followed by frozen section analysis. The results are as follows: Figure 2 As shown, the drug is mainly distributed 10-100 μm below the vascular endothelium, enabling in situ treatment of smooth muscle and inflammatory cells.

[0056] Comparative Example 1: 1 mL of 10 mg / mL mesoporous silica (particle size 200 nm) aqueous dispersion was mixed with 1 mL of 10 mg / mL tocilizumab aqueous solution, incubated for 24 h, and then centrifuged at 12000 rpm to obtain drug-loaded mesoporous silica.

[0057] Drug-loaded mesoporous silica was uniformly dispersed in water to obtain a drug-loaded mesoporous silica solution with a concentration of 0.5 mg / mL.

[0058] A liquid-perfusion balloon is delivered into the blood vessel and pressurized to 8 atm to ensure it adheres tightly to the vessel wall. Next, a drug-loaded mesoporous silica solution is infused into the space between the two balloon layers of the liquid-perfusion balloon, and the pressure is increased to 10 atm. The drug is then expelled from the micropores on the surface of the liquid-perfusion balloon into the blood vessel, delivering a volume of 100 μL.

[0059] Comparative Example 2: 1 mL of amino-modified mesoporous silica aqueous dispersion prepared according to Example 1 (10 mg / mL) was mixed with 1 mL of tocilizumab aqueous solution (10 mg / mL), incubated for 24 h, and then centrifuged at 12000 rpm to obtain drug-loaded mesoporous silica.

[0060] Drug-loaded mesoporous silica was uniformly dispersed in water to obtain a drug-loaded mesoporous silica solution with a concentration of 0.5 mg / mL.

[0061] A liquid-perfusion balloon is delivered into the blood vessel and pressurized to 8 atm to ensure it adheres tightly to the vessel wall. Next, a drug-loaded mesoporous silica solution is infused into the space between the two balloon layers of the liquid-perfusion balloon, and the pressure is increased to 10 atm. The drug is then expelled from the micropores on the surface of the liquid-perfusion balloon into the blood vessel, delivering a volume of 100 μL.

[0062] Blood vessels were removed after 3 days, 1 week, and 4 weeks of delivery in Example 1 and Comparative Examples 1 and 2. After homogenization, the drug retention was tested using an ELISA kit, and the results are as follows: Figure 3 As shown in Example 1, more than 50% of the drug remained in the blood vessels after 4 weeks of drug delivery, achieving long-term sustained release of the drug. In contrast, for Comparative Examples 1 and 2, 35% and 40% of the drug was lost, respectively, 3 days after delivery; 60% and 70% of the drug was lost, respectively, after 1 week; and almost no drug remained after 4 weeks.

[0063] Example 2: 1 g of hexadecyltrimethylammonium chloride and 10 mg of triethanolamine were added to 100 mL of water and stirred until homogeneous. 10 g of tetraethyl orthosilicate was added to the bottom of the aqueous solution and reacted at 60 °C for 8 h to obtain mesoporous silica.

[0064] In an ethanol / water mixture with a volume ratio of 80 / 20, 1 g of mesoporous silica was mixed with 0.3 g of glycidyl etheroxypropyltrimethoxysilane and reacted at room temperature for 12 h. The pH of the reaction was adjusted to 6.0 with hydrochloric acid to obtain epoxy-modified mesoporous silica.

[0065] In a methanol / water mixture with a volume ratio of 50 / 50, 1 g of epoxy-modified mesoporous silica was mixed with 0.1 g of 3-aminophenylboronic acid and reacted at room temperature for 12 h. The reaction pH was 6.0 (adjusted with hydrochloric acid) to obtain a mesoporous silica drug carrier.

[0066] Mix 1 mL of 10 mg / mL mesoporous silica drug carrier ethanol dispersion with 1 mL of 10 mg / mL rapamycin ethanol solution, incubate for 24 h, and then centrifuge at 12000 rpm to obtain drug-loaded mesoporous silica.

[0067] Drug-loaded mesoporous silica was uniformly dispersed in water to obtain a drug-loaded mesoporous silica solution with a concentration of 0.5 mg / mL.

[0068] A liquid-perfusion balloon is delivered into the blood vessel and pressurized to 8 atm to ensure it adheres tightly to the vessel wall. Next, a drug-loaded mesoporous silica solution is infused into the space between the two balloon layers of the liquid-perfusion balloon, and the pressure is increased to 10 atm. The drug is then expelled from the micropores on the surface of the liquid-perfusion balloon into the blood vessel, delivering a volume of 100 μL.

[0069] Example 3: In an ethanol / water mixture with a volume ratio of 80 / 20, 1 g of mesoporous silica was mixed with 0.7 g of methacryloyloxypropyltrimethoxysilane and reacted at room temperature for 12 h (the pH of the reaction was adjusted to 6.0 with hydrochloric acid) to obtain double-bond modified mesoporous silica.

[0070] In a methanol / water mixture with a volume ratio of 50 / 50, 1 g of double-bond modified mesoporous silica was mixed with 0.4 g of 3-aminophenylboronic acid and reacted at 60 °C for 12 h. The pH of the reaction was adjusted to 9.0 with sodium hydroxide to obtain a mesoporous silica drug carrier.

[0071] 1 mL of 10 mg / mL mesoporous silica drug carrier aqueous dispersion was mixed with 1 mL of 10 nmol / mL miR-22 aqueous solution, incubated for 24 h, and then centrifuged at 12000 rpm to obtain drug-loaded mesoporous silica.

[0072] Drug-loaded mesoporous silica was uniformly dispersed in water to obtain a drug-loaded mesoporous silica solution with a concentration of 0.5 mg / mL.

[0073] A liquid-perfusion balloon is delivered into the blood vessel and pressurized to 8 atm to ensure it adheres tightly to the vessel wall. Next, a drug-loaded mesoporous silica solution is infused into the space between the two balloon layers of the liquid-perfusion balloon, and the pressure is increased to 10 atm. The drug is then expelled from the micropores on the surface of the liquid-perfusion balloon into the blood vessel, delivering a volume of 100 μL.

[0074] Furthermore, it should be understood that after reading the above description of the present invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for preparing a mesoporous silica drug carrier for long-term intravascular retention, characterized in that, include: Mesoporous silica is reacted with a functionalized silane coupling agent to obtain surface-functionalized mesoporous silica, and the surface-functionalized mesoporous silica is reacted with phenylboronic acid molecules to obtain the mesoporous silica drug carrier.

2. The method for preparing a mesoporous silica drug carrier for long-term intravascular retention according to claim 1, characterized in that, The reaction between the mesoporous silica and the functionalized silane coupling agent is that the functionalized silane coupling agent is hydrolyzed and / or alcoholized and then condensed with the hydroxyl groups on the surface of the mesoporous silica, thereby grafting onto the surface of the mesoporous silica to form surface-functionalized mesoporous silica. The reaction of mesoporous silica with functionalized silane coupling agent is as follows: the pH of the reaction system is 4~6.5, the reaction temperature is room temperature~60℃, the reaction time is 2~12 h, the mass ratio of mesoporous silica to functionalized silane coupling agent is 1:0.1~1, and the reaction solvent includes water and / or ethanol. The surface-functionalized mesoporous silica reacts with phenylboronic acid molecules in the following ways: the pH of the reaction system is 4-10, the reaction temperature is room temperature to 60°C, the reaction time is 0.5-12 h, the mass ratio of surface-functionalized mesoporous silica to phenylboronic acid molecules is 1:0.1-0.5, and the reaction solvent includes water and / or methanol. The functionalized silane coupling agent includes at least one of 3-aminopropyltriethoxysilane, glycidoxypropyltrimethoxysilane, methacryloyloxypropyltrimethoxysilane, and 3-mercaptopropyltrimethoxysilane. The phenylboronic acid molecules include at least one of 4-formylphenylboronic acid, 3-formylphenylboronic acid, 2-formylphenylboronic acid, 4-carboxyphenylboronic acid, 3-carboxyphenylboronic acid, 2-carboxyphenylboronic acid, 4-aminophenylboronic acid, 3-aminophenylboronic acid, 2-aminophenylboronic acid, 4-allylphenylboronic acid, 3-allylphenylboronic acid, and 2-allylphenylboronic acid; The mesoporous silica has a particle size of 20~1000 nm.

3. The mesoporous silica drug carrier prepared by the preparation method according to claim 1 or 2.

4. The mesoporous silica drug carrier according to claim 3 is used for loading drugs.

5. A pharmaceutical complex, characterized in that, Includes the mesoporous silica drug carrier of claim 3 and the drug loaded on the mesoporous silica drug carrier.

6. The method for preparing the drug complex according to claim 5, characterized in that, include: The drug is mixed with the mesoporous silica drug carrier in a solvent and incubated for a period of time to obtain the drug complex.

7. A drug complex dispersion, characterized in that, Includes a dispersant and a pharmaceutical complex according to claim 5, uniformly dispersed in the dispersant.

8. The method for preparing the drug complex dispersion according to claim 7, characterized in that, include: The drug complex is uniformly dispersed in a dispersant to obtain a drug complex dispersion.

9. The use of the mesoporous silica drug carrier according to claim 3 or the drug complex dispersion according to claim 7 in a liquid perfusion balloon.

10. A liquid perfusion balloon containing the drug complex dispersion of claim 7.

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