Drug carrying device for forming in-situ intravascular stent and preparation method

Abstract

The invention discloses a medicine carrying device for forming an in-situ intravascular stent and a preparation method. The medicine carrying device comprises an interventional instrument and a medicine coating covering the surface of the interventional instrument; the raw materials of the drug coating comprise a photoactive cross-linking agent and amino acid polyethylene glycol, and the mass ratio of the photoactive cross-linking agent to the amino acid polyethylene glycol is (0.5-2.5): 1; the photoactive cross-linking agent is selected from at least one of a naphthalimide derivative, rose bengal and riboflavin phosphate; the molecular weight of the amino acid polyethylene glycol is 1000-20000, and the amino acid group contained in the amino acid polyethylene glycol corresponds to at least one of tyrosine, tryptophan, histidine, lysine, arginine, methionine and cysteine. According to the medicine carrying device for forming the in-situ intravascular stent, after amino acid polyethylene glycol is added, amino acid residues at the two ends are subjected to light activation, protein which is not adjacent to the position of a vascular wall is also subjected to crosslinking, and a natural intravascular stent with denser fibers is formed through crosslinking.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and in particular to a drug-carrying device and a preparation method for forming an in-situ vascular stent. Background Art

[0002] Angioplasty balloons can be used to open calcified lesions in arterial walls and are one of the main ways to revascularize arterial stenosis. However, when blood vessels are dilated, they cause damage to the vessel wall, which can trigger thrombosis and the release of growth factors, which can lead to restenosis or subsequent reclosure of the dilated vessel.

[0003] At present, the emerging treatment method is natural vascular stent, that is, balloon dilatation catheter with photosensitive compounds or drugs. Unlike traditional drug balloons, the balloon part of this type of balloon dilatation catheter can scatter visible light, so that the photosensitive compound is excited, thereby inducing the rapid combination of collagen and elastin in the blood vessel wall, forming a stent in situ, and achieving blood vessel healing and repair. However, in this treatment plan, the photosensitive compound can only induce the cross-linking of adjacent collagen and elastin in the blood vessel wall, and the in situ stent fiber structure is loose, which affects the effect of angioplasty. Summary of the invention

[0004] In order to solve the above problems, the present application provides a drug-carrying device for cross-linking non-adjacent collagen and elastin to form an in situ vascular stent.

[0005] The drug-carrying device for forming an in situ vascular stent provided in the present application comprises an interventional device and a drug coating covering the surface of the interventional device; the raw materials of the drug coating comprise a photoactive crosslinking agent and amino acid-modified polyethylene glycol, and the mass ratio of the photoactive crosslinking agent to the amino acid-modified polyethylene glycol is 0.5 to 2.5:1;

[0006] The photoactive crosslinking agent is selected from at least one of naphthalimide derivatives, rose bengal, and riboflavin phosphate; the molecular weight of the amino acid-modified polyethylene glycol is 1000-20000, and the amino acid group contained corresponds to at least one of tyrosine, tryptophan, histidine, lysine, arginine, methionine, and cysteine.

[0007] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution, but are merely further supplements or preferences. Under the premise that there are no technical or logical contradictions, each optional method can be combined with the above-mentioned overall solution separately, and multiple optional methods can also be combined.

[0008] Optionally, the raw materials of the drug coating also include a drug agent, and the drug agent is at least one of rapamycin, sirolimus, everolimus, zotarolimus, 42-(dimethylphosphinate) rapamycin, defostiolimus, biolimus, umimos, tacrolimus, paclitaxel, protaxel, and docetaxel.

[0009] Optionally, the mass ratio of the drug agent to the amino acid-conjugated polyethylene glycol is 1 to 3.5:1.

[0010] Optionally, the raw materials of the drug coating also include a carrier, and the carrier is selected from at least one of polyethylene glycol, polyvinyl alcohol, polyethylene oxide, polysorbate, polyvinyl pyrrolidone, magnesium stearate, urea, tri-n-hexyl butyryl citrate, iopromide, ethyl cellulose, methyl hydroxybenzoate, ethyl hydroxybenzoate, acetyl tributyl citrate, glyceryl stearate, diethyl pyrocarbonate, distearoyl phosphatidylethanolamine-polyethylene glycol, cholesterol, phospholipids, polylactide, polyglycolide, polylactic acid-glycolic acid copolymer, polyorthoester, polyanhydride, polyamino acid, polyhydroxybutyric acid, polyacetal, polycyanoacrylate, polycaprolactone, polydioxanone, polyalkylene polymer, polyalkyl carbonate, gelatin, collagen, alginate, chitin, chitosan, dextran, hyaluronic acid, shellac, and pectin.

[0011] Optionally, the mass ratio of the drug agent to the carrier is 0.5 to 2:1.

[0012] Optionally, the raw materials of the drug coating include, by weight:

[0013]

[0014] Wherein, the amino acid group corresponds to tyrosine or lysine; the molecular weight of the amino acid-converted polyethylene glycol is 2000-8000.

[0015] Optionally, the raw materials of the drug coating include, by weight:

[0016]

[0017] Wherein, the amino acid group corresponds to tyrosine or lysine; and the molecular weight of the amino acid-converted polyethylene glycol is 4000.

[0018] Optionally, the raw materials of the drug coating include, by weight:

[0019]

[0020] Optionally, the interventional device includes a balloon body, a light-guiding element is fixed inside the balloon body; or the light-guiding element can be inserted into the balloon body, and the light-guiding element is used to provide visible light with a wavelength of 400 to 520 nm.

[0021] The present application provides a method for preparing the drug carrying device, comprising the following steps:

[0022] An interventional device is provided, the interventional device comprising a balloon body, the balloon body having a contracted state suitable for interventional delivery and a relatively inflated state; a first drug liquid is sprayed on the surface of the balloon body in the inflated state and dried to obtain a preform, wherein the first drug liquid is prepared by amino acid-modified polyethylene glycol, a photoactive crosslinking agent and a first dispersant;

[0023] The drug-carrying device is obtained by spraying a second drug liquid on the surface of the preform and drying the preform, wherein the second drug liquid is prepared by a carrier, a drug reagent and a second dispersant.

[0024] Optionally, the first dispersant and the second dispersant are each independently selected from at least one of water, methanol, ethanol, formic acid, acetic acid, acetonitrile, isopropanol, acetone, ethyl acetate, n-hexane, cyclohexane, dichloromethane, methyl acetate, butyl acetate, carbon tetrachloride, butanone, n-hexane, n-pentane, and n-heptane.

[0025] Optionally, the spraying amount of the first liquid is 1-10 μg / mm calculated based on the photoactive crosslinking agent. 2 The spraying amount of the second liquid is calculated as 1 to 10 μg / mm 2 .

[0026] Optionally, the first dispersant is water, and the spraying amount of the first liquid is 2-5 μg / mm2 calculated based on the photoactive crosslinking agent. 2 The second dispersant is n-heptane, and the spraying amount of the second liquid is 2 to 5 μg / mm calculated based on the drug reagent. 2 .

[0027] Compared with the prior art, the drug-carrying device for forming an in situ vascular stent disclosed in the present application, after adding amino acid-modified polyethylene glycol, the amino acid residues at both ends can be cross-linked with non-adjacent proteins on the blood vessel wall after light activation, which is equivalent to building a "bridge" between non-adjacent proteins, forming a natural vascular stent with denser fibers, greatly improving the effect of angioplasty. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the angiogram of the left superficial distal femoral vessels before surgery in Application Example 1;

[0029] Figure 2 This is an angiogram of the left superficial distal femoral vessels after surgery in Application Example 1;

[0030] Figure 3 This is the angiography of the left superficial proximal femoral vessels before surgery in comparative example 1;

[0031] Figure 4 This is the angiography of the left superficial proximal femoral vessels after surgery in comparative example 1;

[0032] Figure 5 This is the angiography of the left superficial distal femoral vessels before surgery in comparative example 2;

[0033] Figure 6 This is the angiography of the left superficial distal femoral vessels after surgery in comparative example 2;

[0034] Figure 7 This is the staining image of the left superficial distal femoral blood vessels under the microscope after the operation of Application Example 1;

[0035] Figure 8 This is the staining image of the left superficial distal femoral vascular tissue under a microscope after surgery in comparative example 1.

[0036] Fig. 9 This is the staining image of the left superficial proximal femoral vascular tissue under a microscope after surgery in comparative example 2. DETAILED DESCRIPTION

[0037] 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 only 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 this application.

[0038] The present application discloses a drug-carrying device for forming an in-situ vascular stent, including an interventional device and a drug coating covering the surface of the interventional device;

[0039] The raw materials of the drug coating include a photoactive cross-linking agent and a first polyethylene glycol, and the mass ratio of the photoactive cross-linking agent to the first polyethylene glycol is 0.5-2.5:1, preferably 1:1.

[0040] The photoactive crosslinking agent is selected from at least one of naphthalimide derivatives, rose bengal, and riboflavin phosphate. The molecular weight of the first polyethylene glycol chain is 1000 to 20000, preferably 2000 to 8000. The auxiliary crosslinking agent is a flexible chain with amino acids or polypeptides at both ends. The naphthalimide derivative is a derivative of 4-substituted-1,8-naphthalimide, naphthalimide dimer, etc.

[0041] Therefore, after illumination, not only can the collagen cross-linking on the blood vessel wall be promoted, but also the photoactivators naphthylimide derivatives, rose bengal, and riboflavin phosphate can promote the cross-linking of collagen or other proteins in the blood vessel wall after light activation, forming a stent in situ, and achieving blood vessel healing and repair. Under light excitation, the photoactivated cross-linker is activated to produce a transient singlet excited state, and a triplet excited state intermediate is produced by molecular intersystem crossing. The triplet excited state intermediate undergoes intramolecular charge transfer and enters a long-lived intramolecular charge transfer state. The photoactivator in the triplet excited state converts free oxygen into active oxygen free radicals through photoelectron transfer, and the active oxygen promotes the cross-linking reaction of oxidizable amino acid residues (such as tyrosine, tryptophan, histidine, methionine, and cysteine).

[0042] After being activated by light, photoactivators can only promote the cross-linking of adjacent collagen or other proteins. After the addition of amino acid-modified polyethylene glycol, the amino acid groups connected at both ends of the polyethylene glycol, such as the amino group, can also undergo condensation reactions with amino acid residues on the blood vessel wall, such as the carboxyl group and N-hydroxysuccinimide, under photoactivation, thereby promoting the cross-linking of proteins. This is equivalent to building a "bridge" between non-adjacent proteins. After photoactivation, non-adjacent proteins can also be cross-linked. In this way, the natural vascular stent formed in situ has denser fibers, greatly improving the effect of angioplasty.

[0043] The raw materials of the drug coating also include drug agents, which can inhibit the intimal hyperplasia caused by excessive proliferation of smooth muscle cells, thereby inhibiting the proliferation of endothelial cells, and have the effect of preventing and treating vascular restenosis. The drug agent is a cell growth inhibitory drug or an antiproliferative drug. The drug agent is at least one of rapamycin, sirolimus, everolimus, zotarolimus, 42-(dimethylphosphinate) rapamycin (deforolimus), deforolimus, biolimus, umirolimus, tacrolimus, paclitaxel, protaxel and docetaxel. Among them, rapamycin, sirolimus, everolimus, zotarolimus, 42-(dimethylphosphinate) rapamycin, deforolimus, biolimus, umirolimus and tacrolimus are cell growth inhibitory drugs, and paclitaxel, protaxel and docetaxel are antiproliferative drugs.

[0044] In the drug coating material, the mass ratio of the drug agent to the amino acid-modified polyethylene glycol is (1-3.5):1, preferably 2:3.

[0045] The raw materials of the drug coating also include a carrier, and the carrier is selected from at least one of a second polyethylene glycol, polyvinyl alcohol, polyethylene oxide, polysorbate, polyvinyl pyrrolidone, magnesium stearate, urea, tri-n-hexyl butyryl citrate, iopromide, ethyl cellulose, methyl hydroxybenzoate, ethyl hydroxybenzoate, acetyl tributyl citrate, glyceryl stearate, diethyl pyrocarbonate, distearoyl phosphatidylethanolamine-polyethylene glycol, cholesterol, phospholipids, polylactide, polyglycolide, polylactic acid-glycolic acid copolymer, polyorthoester, polyanhydride, polyamino acid, polyhydroxybutyric acid, polyacetal, polyacrylic acid cyanoester, polycaprolactone, polydioxanone, polyalkylene alkylate, polyalkyl carbonate, gelatin, collagen, fibric acid, alginic acid, chitin, chitosan, dextran, hyaluronic acid, shellac, and pectin.

[0046] The mass ratio of the drug agent to the carrier in the drug coating material is (0.5-2):1, preferably 0.9:1.

[0047] In a preferred embodiment, the raw materials of the drug coating include, by weight:

[0048]

[0049] The drug-carrying device for forming an in-situ vascular stent provided in the embodiment of the present application includes a balloon body, and a light-guiding element is fixedly provided on the balloon body; or a light-guiding element can penetrate into the balloon body. After the light-guiding element is connected to a light source, it can emit visible light with a wavelength of 400 to 520 nm to activate the photoactive crosslinking agent to react.

[0050] An embodiment of the present application further discloses a method for preparing an in-situ vascular stent drug-carrying device, comprising the following steps:

[0051] An interventional device is provided, the interventional device includes a balloon body, the balloon body has a contracted state suitable for interventional delivery and a relatively inflated state; a first drug liquid is sprayed on the surface of the balloon body in the inflated state and dried to obtain a preform, the first drug liquid is prepared by amino acid-modified polyethylene glycol, a photoactive crosslinking agent and a first dispersant;

[0052] The second drug liquid is sprayed on the surface of the preform and dried to obtain a drug-carrying device, wherein the second drug liquid is prepared by a carrier, a drug reagent and a second dispersant.

[0053] The first liquid and the second liquid may be applied by spraying or dipping.

[0054] The first dispersant and the second dispersant are each independently selected from at least one of water, methanol, ethanol, formic acid, acetic acid, acetonitrile, isopropanol, acetone, ethyl acetate, n-hexane, cyclohexane, dichloromethane, methyl acetate, butyl acetate, carbon tetrachloride, butanone, n-hexane, n-pentane, and n-heptane.

[0055] The spraying amount of the first liquid is 1-10 μg / mm calculated as the photoactive crosslinking agent. 2 The spraying amount of the second liquid is calculated as 1-10 μg / mm 2 .

[0056] Preferably, the first dispersant is water, and the spraying amount of the first liquid is 2-5 μg / mm 2 The second dispersant is n-heptane, and the spraying amount of the second liquid is 2-5 μg / mm calculated based on the drug reagent. 2 .

[0057] Preparation Example 1 Preparation of a drug-carrying device for forming an in situ vascular stent

[0058] (1) Prepare the first liquid medicine:

[0059] 32 mg of amino acid-modified polyethylene glycol (lysine-PEG-lysine), which is a commercially available reagent with a molecular weight of 4000, was added to 2 mL of water and mixed thoroughly; then 32 mg of riboflavin sodium phosphate was added and mixed by ultrasonic oscillation to prepare the first drug solution.

[0060] (2) Preparation of the second liquid:

[0061] 40 mg of phospholipid and 5 mg of cholesterol were dissolved in 5 mL of n-heptane, and after ultrasonic oscillation and mixing, 50 mg of rapamycin was added, and vortex ultrasonic dispersion was performed to prepare the second drug solution.

[0062] (3) First, spray the first liquid on the surface of the balloon (inflated state) and dry it. The spraying amount is 3 μg / mm based on riboflavin sodium phosphate. 2 , the thickness of the first liquid coating formed is 14 μm;

[0063] The second liquid was sprayed on the first liquid coating and dried. The spraying amount was 2 μg / mm2 based on rapamycin. 2 The thickness of the second chemical liquid coating formed is 10 μm.

[0064] (4) The balloon is evacuated and folded into petals, and then heat-set at 50°C for 10 min to obtain a drug-loaded balloon.

[0065] Preparation Example 2 Preparation of a drug-carrying device for forming an in situ vascular stent

[0066] (1) Prepare the first liquid medicine:

[0067] 16 mg of amino acid-modified polyethylene glycol (lysine-PEG-lysine), which is a commercially available reagent with a molecular weight of 4000, was added to 2 mL of water and mixed thoroughly; then 32 mg of riboflavin sodium phosphate was added and mixed by ultrasonic oscillation to prepare the first drug solution.

[0068] (2) Preparation of the second liquid:

[0069] 40 mg of phospholipid and 5 mg of cholesterol were dissolved in 5 mL of n-heptane, and after ultrasonic oscillation and mixing, 50 mg of rapamycin was added, and vortex ultrasonic dispersion was performed to prepare the second drug solution.

[0070] (3) First, spray the first liquid on the surface of the balloon (inflated state) and dry it. The spraying amount is 3 μg / mm based on riboflavin sodium phosphate. 2 , the thickness of the first liquid coating formed is 12 μm;

[0071] The second liquid was sprayed on the first liquid coating and dried. The spraying amount was 2 μg / mm2 based on rapamycin. 2 The thickness of the second chemical liquid coating formed is 10 μm.

[0072] (4) The balloon is evacuated and folded into petals, and then heat-set at 50°C for 10 min to obtain a drug-loaded balloon.

[0073] Preparation Example 3 Preparation of a drug-carrying device for forming an in situ vascular stent

[0074] (1) Prepare the first liquid medicine:

[0075] 48 mg of amino acid-modified polyethylene glycol (lysine-PEG-lysine), a commercially available reagent with a molecular weight of 4000, was added to 2 mL of water and mixed thoroughly; then 32 mg of riboflavin sodium phosphate was added and mixed by ultrasonic oscillation to prepare the first drug solution.

[0076] (2) Preparation of the second liquid:

[0077] 40 mg of phospholipid and 5 mg of cholesterol were dissolved in 5 mL of n-heptane, and after ultrasonic oscillation and mixing, 50 mg of rapamycin was added, and vortex ultrasonic dispersion was performed to prepare the second drug solution.

[0078] (3) First, spray the first liquid medicine on the surface of the balloon (inflated state) and dry it. Then, spray the first polyethylene glycol at a rate of 3 μg / mm 2 , the thickness of the first liquid coating formed is 14 μm;

[0079] The second liquid was sprayed on the first liquid coating and dried. The spraying amount was 2 μg / mm2 based on rapamycin. 2 The thickness of the second chemical liquid coating formed is 10 μm.

[0080] (4) The balloon is evacuated and folded into petals, and then heat-set at 50°C for 10 min to obtain a drug-loaded balloon.

[0081] Preparation Example 4 Preparation of a drug-carrying device for forming an in situ vascular stent

[0082] (1) Prepare the first liquid medicine:

[0083] 32 mg of riboflavin sodium phosphate was thoroughly mixed with 2 mL of water to prepare the first drug solution.

[0084] (2) Preparation of the second liquid:

[0085] 40 mg of phospholipid and 5 mg of cholesterol were dissolved in 5 mL of n-heptane, and after ultrasonic oscillation and mixing, 50 mg of rapamycin was added, and vortex ultrasonic dispersion was performed to prepare the second drug solution.

[0086] (3) First, spray the first liquid on the surface of the balloon (inflated state) and dry it. The spraying amount is 3 μg / mm based on riboflavin sodium phosphate. 2 , the thickness of the first liquid coating formed is 12 μm;

[0087] The second liquid was sprayed on the first liquid coating and dried. The spraying amount was 2 μg / mm2 based on rapamycin. 2 The thickness of the second chemical liquid coating formed is 10 μm.

[0088] (4) The balloon is evacuated and folded into petals, and then heat-set at 50°C for 10 min to obtain a drug-loaded balloon.

[0089] Preparation Example 5 Preparation of a common drug balloon

[0090] (1) Dissolve 40 mg of phospholipid and 5 mg of cholesterol in 5 mL of n-heptane, mix by ultrasonic oscillation, add 50 mg of rapamycin, and disperse by vortex ultrasonication to prepare a drug solution.

[0091] (2) Spray the drug solution on the surface of the balloon (inflated state) and dry it. The spraying amount is 2 μg / mm2 based on rapamycin. 2 The thickness of the formed drug solution coating is 10μm.

[0092] The balloon was evacuated and folded into petals, and then heat-set at 50°C for 10 min to obtain a drug-loaded balloon.

[0093] Application Example 1

[0094] The effectiveness of the drug balloon was studied using a porcine peripheral artery model. In the porcine peripheral artery model, the balloon of Preparation Example 1 was pushed into the blood vessel, and the compressed balloon was expanded by perfusing fluid at a pressure of 6 atm. Then, while maintaining the pressure of the balloon, the light-guiding element emitted light of 450 nm wavelength, and the light curing time was 3 minutes. After illumination, the balloon was withdrawn from the blood vessel. After 28 days, the vascular lumen gain was measured by contrast imaging, and the tissue layer, fiber distribution or cell morphology of each sample tissue section after HE staining were observed under a microscope.

[0095] Comparative Example 1

[0096] The effectiveness of the drug balloon was studied using a porcine peripheral artery model. In the porcine peripheral artery model, the balloon of Preparation Example 4 was pushed into the blood vessel, and the compressed balloon was expanded by perfusing fluid at a pressure of 6 atm. Then, while maintaining the pressure of the balloon, the light-guiding element emitted light of 450 nm wavelength, and the light curing time was 3 minutes. After illumination, the balloon was withdrawn from the blood vessel. After 28 days, the vascular lumen gain was measured by contrast imaging, and the tissue layer, fiber distribution or cell morphology of each sample tissue section after HE staining were observed under a microscope.

[0097] Comparative Example 2

[0098] The effectiveness of the drug balloon was studied using a porcine peripheral artery model. In the porcine peripheral artery model, the balloon of Preparation Example 5 was pushed into the blood vessel, and the compressed balloon was expanded by perfusing fluid at a pressure of 6 atm, and then the balloon pressure was maintained. After 28 days, the vascular lumen gain was measured by contrast imaging, and the tissue layer, fiber distribution or cell morphology of each sample tissue section after HE staining was observed under a microscope.

[0099] Table 1 Vascular lumen gain

[0100]

[0101] The effect of this application is that the vascular lumen gain retention is increased, by Figures 1 to 6 As shown in Table 1, the 28-day vascular lumen gain rate of Application Example 1 is as high as 43.92%, which is almost twice that of Comparative Example 1 and more than three times that of Comparative Example 2, proving that the in situ vascular stent drug-carrying device of the present invention can effectively increase the postoperative vascular lumen gain retention; Figures 7 to 9 As shown, compared with Comparative Examples 1 and 2, the vascular fibers after treatment in Application Example 1 are more uniform and dense, the tissue damage is slight, the repair effect is significant, and the blood vessels are effectively protected from tearing during expansion.

[0102] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0103] The above embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. A drug-carrying device for forming an in-situ vascular stent, characterized in that: It comprises an interventional device and a drug coating covering the surface of the interventional device; the raw materials of the drug coating include a photoactive cross-linking agent and amino acid-modified polyethylene glycol, and the mass ratio of the photoactive cross-linking agent to the amino acid-modified polyethylene glycol is 0.5-2.5:1; The photoactive crosslinking agent is selected from at least one of naphthalimide derivatives, rose bengal, and riboflavin phosphate; the molecular weight of the amino acid-modified polyethylene glycol is 1000-20000, and the amino acid group contained corresponds to at least one of tyrosine, tryptophan, histidine, lysine, arginine, methionine, and cysteine.

2. The drug-carrying device for forming an in-situ vascular stent according to claim 1, characterized in that: The raw materials of the drug coating also include a drug agent, and the drug agent is at least one of rapamycin, sirolimus, everolimus, zotarolimus, 42-(dimethylphosphinate) rapamycin, rifoslimus, biolimus, umimos, tacrolimus, paclitaxel, protaxel, and docetaxel; The mass ratio of the drug agent to the amino acid-modified polyethylene glycol is 1 to 3.5:

1.

3. The drug-carrying device for forming an in-situ vascular stent according to claim 2, characterized in that: The raw materials of the drug coating also include a carrier, and the carrier is selected from at least one of polyethylene glycol, polyvinyl alcohol, polyethylene oxide, polysorbate, polyvinyl pyrrolidone, magnesium stearate, urea, tri-n-hexyl butyryl citrate, iopromide, ethyl cellulose, methyl hydroxybenzoate, ethyl hydroxybenzoate, acetyl tributyl citrate, glyceryl stearate, diethyl pyrocarbonate, distearoyl phosphatidylethanolamine-polyethylene glycol, cholesterol, phospholipids, polylactide, polyglycolide, polylactic acid-glycolic acid copolymer, polyorthoester, polyanhydride, polyamino acid, polyhydroxybutyric acid, polyacetal, polycyanoacrylate, polycaprolactone, polydioxanone, polyalkylene polymer, polyalkyl carbonate, gelatin, collagen, alginate, chitin, chitosan, dextran, hyaluronic acid, shellac, and pectin; the mass ratio of the drug agent to the carrier is 0.5 to 2:

1.

4. The drug-carrying device for forming an in-situ vascular stent according to claim 3, characterized in that: In parts by weight, the raw materials of the drug coating include: Wherein, the amino acid group corresponds to tyrosine or lysine; the molecular weight of the amino acid-converted polyethylene glycol is 2000-8000.

5. The drug-carrying device for forming an in-situ vascular stent according to claim 4, characterized in that: In parts by weight, the raw materials of the drug coating include: Wherein, the amino acid group corresponds to tyrosine or lysine; the molecular weight of the amino acid-converted polyethylene glycol is 4000.

6. The drug-carrying device for forming an in-situ vascular stent according to claim 5, characterized in that: In parts by weight, the raw materials of the drug coating include:

7. The drug-carrying device for forming an in-situ vascular stent according to claim 1, characterized in that: The interventional instrument comprises a balloon body, a light-guiding element is fixed inside the balloon body, or the light-guiding element can penetrate into the balloon body, and the light-guiding element is used to provide visible light with a wavelength of 400 to 520 nm.

8. The method for preparing a drug-carrying device according to any one of claims 3 to 7, characterized in that: The following steps are involved: An interventional device is provided, the interventional device comprising a balloon body, the balloon body having a contracted state suitable for interventional delivery and a relatively inflated state; a first drug liquid is sprayed on the surface of the balloon body in the inflated state and dried to obtain a preform, wherein the first drug liquid is prepared by amino acid-modified polyethylene glycol, a photoactive crosslinking agent and a first dispersant; The drug-carrying device is obtained by spraying a second drug liquid on the surface of the preform and drying the preform, wherein the second drug liquid is prepared by a carrier, a drug reagent and a second dispersant.

9. The method for preparing the drug carrying device according to claim 8, characterized in that: The first dispersant and the second dispersant are each independently selected from at least one of water, methanol, ethanol, formic acid, acetic acid, acetonitrile, isopropanol, acetone, ethyl acetate, n-hexane, cyclohexane, dichloromethane, methyl acetate, butyl acetate, carbon tetrachloride, butanone, n-hexane, n-pentane, and n-heptane; The spraying amount of the first liquid is 1-10 μg / mm calculated based on the photoactive crosslinking agent. 2 The spraying amount of the second liquid is calculated as 1 to 10 μg / mm 2 .

10. The method for preparing a drug carrying device according to claim 9, characterized in that: The first dispersant is water, and the spraying amount of the first liquid is 2-5 μg / mm calculated based on the photoactive crosslinking agent. 2 The second dispersant is n-heptane, and the spraying amount of the second liquid is 2 to 5 μg / mm calculated based on the drug reagent. 2 .

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