Photosensitive material with vascular repair function, preparation method thereof and balloon dilatation catheter

Abstract

The application relates to the technical field of medical materials, and discloses photosensitive material with a blood vessel repair function, a preparation method of the photosensitive material and a balloon dilatation catheter. The photosensitive material with the blood vessel repair function is obtained by splicing water-soluble DNA and photosensitive compounds through a chemical bond, does not affect the photosensitivity of the material, can quickly dissolve, permeate and diffuse into a blood vessel wall after reaching a lesion site, and has the advantages that increasing the water solubility is beneficial to metabolism of subsequent small molecules, reduces accumulation toxicity caused by large-dose application of small molecule drugs due to low solubility, the material is activated by specific wavelength light, covalent crosslinking between amino acids in the blood vessel wall is generated, the blood vessel is stably supported, in-stent restenosis does not occur, the treatment purpose can be well achieved after 1-minute balloon rapid expansion, the operation risk is greatly reduced, and the survival rate of patients is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a photosensitive material with a blood vessel repair function, a preparation method thereof, and a balloon dilatation catheter. Background Art

[0002] Angioplasty is a minimally invasive procedure in which a balloon dilatation catheter is delivered to the site of vascular lesions when a blood vessel is narrowed. The balloon is expanded by applying external pressure, thereby dilating the blood vessel and improving blood flow. Dilating the blood vessels in this way can easily cause immediate elastic retraction or occlusion of the blood vessels, or the endothelium of the blood vessels may be torn or damaged during dilation, leading to immediate stenosis.

[0003] To solve the above problems, relevant technologies propose to implant natural vascular stents in blood vessels. This technology is to coat the balloon with a small molecule coating. After the balloon is expanded, the small molecule drug is released to the inner wall of the blood vessel. It is activated by light of a specific wavelength (450nm) to cause the amino acids in the inner wall of the blood vessel to form covalent cross-links, which has a supporting effect on the blood vessel, thereby avoiding the problem of blood vessel retraction.

[0004] Related research has demonstrated that 4-substituted 1,8-naphthalimide molecules can be used for protein bonding, acting as natural vascular stents. Different substituents at the 4-position have demonstrated excellent protein bonding. 1,8-naphthalimide molecules have been widely used in photocrosslinking research, and numerous modifications have been reported. However, 1,8-naphthalimide dimers have poor water solubility. Consequently, when using 1,8-naphthalimide dimers as photosensitive materials for vasodilatory surgery, they require 5 minutes of exposure to the vessel wall to penetrate and photocrosslink. Prolonged blood flow occlusion significantly increases surgical risk. Traditionally, salts have been used to increase the water solubility of compounds, but the resulting pH shift can affect the photobonding efficacy of 1,8-naphthalimide dimers. Literature studies have shown that 1,8-naphthalimide exhibits optimal photobonding efficacy at a pH of 10. However, the most commonly used method, converting 1,8-naphthalimide to acetate, fails to achieve both high water solubility and a pH of approximately 10, compromising therapeutic efficacy. Summary of the Invention

[0005] In view of this, the present invention provides a photosensitive material with vascular repair function and a preparation method thereof. After reaching the lesion site, the material can quickly dissolve, release and diffuse into the cell wall, stably supporting the blood vessels and avoiding the problem of vascular retraction.

[0006] To achieve the above objectives, the present invention provides the following technical solutions:

[0007] In a first aspect, the present invention provides a photosensitive material having a vascular repair function, having a structure as shown in Formula I:

[0008]

[0009] wherein n is an integer of 1 to 6; R1 is at least one of substituted or unsubstituted C1-C10 alkylene, -C(O)-, -R3C(O)-, and -C(O)NHR4C(O)-; R3 and R4 are independently selected from substituted or unsubstituted C1-C10 alkylene;

[0010] R2 is a DNA comprising a connecting segment having a structure as shown in Formula II or Formula III, wherein the imino group connects to the R1:

[0011]

[0012] In some alternative embodiments, the DNA comprises 12-16 bases.

[0013] In some optional embodiments, the molecular weight of the DNA is 4500-5300.

[0014] In some optional embodiments, the structural formula of the DNA is as follows:

[0015]

[0016] In some optional embodiments, R1, R3, and R4 are independently selected from C1-C7 alkylene.

[0017] In some optional embodiments, the substituent in the substituted C1-C10 alkylene group includes halogen, and the halogen is at least one of fluorine, chlorine, bromine, and iodine.

[0018] In some optional embodiments, the chemical structure of the photosensitive material includes:

[0019]

[0020]

[0021]

[0022] In a second aspect, the present invention provides a method for preparing the photosensitive material having vascular repair function according to the first aspect, comprising method one, method two, method three or method four, wherein:

[0023] When R1 is a substituted or unsubstituted C1-C10 alkylene group, the preparation method 1 comprises the following steps:

[0024] (1) 1,8-naphthalimide dimer reacts with Br-R1-Cl to obtain intermediate a;

[0025] (2) reacting the intermediate a with R2H to obtain;

[0026] When R1 is -R3CO-, the preparation method 2 is adopted, comprising the following steps:

[0027] (1) reacting R2H with a halogenated acyl halide to obtain intermediate b;

[0028] (2) The intermediate b is reacted with 1,8-naphthalimide dimer to obtain;

[0029] When R1 is -CONHR4CO-, the preparation method 3 is adopted, comprising the following steps:

[0030] (1) reacting R2H with an amino acid containing an amino protecting group to obtain intermediate c;

[0031] (2) reacting the intermediate c with a deprotecting agent to obtain the intermediate d;

[0032] (3) The intermediate d, 1,8-naphthaleneimide dimer and N,N'-succinimidyl carbonate are reacted to obtain the product;

[0033] When R1 is -CO-, the preparation method 4 is adopted, comprising the following steps:

[0034] R2H, N,N'-succinimidyl carbonate and 1,8-naphthalimide dimer are reacted to form urea to obtain;

[0035] The molecular structure of the 1,8-naphthalimide dimer is as follows:

[0036]

[0037] In some optional embodiments, the Br-R1-Cl includes at least one of 1-bromo-2-chloroethane, 1-chloro-2-bromopropane, 1-bromo-3-chloropropane, 1-bromo-3-chloro-2-methylpropane, 1-bromo-3-chlorocyclobutane, 1-bromo-4-chlorobutane, 1-bromo-4-chloropentane, 1-bromo-5-chloropentane, 1-bromo-6-chlorohexane, 1-bromo-7-chloroheptane, 1-bromo-8-chlorooctane, 1-bromo-10-chlorodecane, trans-3-bromo-1-chloro-1-propene, trans-1-bromo-4-chloro-2-butene, and 1-chloro-4-bromo-2-butanone.

[0038] In some optional embodiments, the halogenated acyl halide includes at least one of chloroacetyl chloride, 2-chloropropionyl chloride, 3-chloropropionyl chloride, chlorobutyryl chloride, chlorovaleryl chloride, and chlorohexanoyl chloride.

[0039] In some optional embodiments, the amino acid includes at least one of glycine, tyrosine, alanine, and 5-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pentanoic acid.

[0040] In some optional embodiments, the deprotection reagent includes at least one of piperidine and trifluoroacetic acid.

[0041] In a third aspect, the present invention provides a photosensitive material with vascular repair function as described in the first aspect, or a photosensitive material prepared by the method as described in the second aspect, and its use in preparing a drug for treating vascular stenosis or occlusion.

[0042] In a fourth aspect, the present invention provides a balloon dilatation catheter comprising a balloon body; the surface of the balloon body has a coating, the coating comprising an adhesive and the photosensitive material with vascular repair function described in the first aspect or a photosensitive material prepared by the method described in the second aspect.

[0043] In some alternative embodiments, the adhesive comprises shellac.

[0044] In some optional embodiments, the mass ratio of the adhesive to the photosensitive material is 0.1-1:0.1-4.

[0045] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0046] 1. The photosensitive material with vascular repair function provided by the present invention splices water-soluble DNA and photosensitive compounds through chemical bonds, which does not affect the photosensitivity of the material, so that the photosensitive material can quickly dissolve, penetrate and diffuse into the blood vessel wall after reaching the lesion site. At the same time, increasing its water solubility is also beneficial to the subsequent metabolism of small molecules, reducing the cumulative toxicity caused by the large-dose application of small molecule drugs due to low solubility. The material is activated by light of a specific wavelength and then induces covalent cross-linking between amino acids in the blood vessel wall, stably supporting the blood vessels, which is equivalent to forming a natural and stable invisible stent. There is no foreign body in the blood vessel, and no restenosis in the stent will occur. After rapid balloon expansion for 1 minute, the treatment purpose can be well achieved, greatly reducing the risk of surgery and improving the survival rate of patients.

[0047] 2. The balloon dilatation catheter provided by the present invention includes an adhesive and a photosensitive material, wherein the adhesive includes shellac. The photosensitive material prepared by the present invention has good water solubility, which may result in the photosensitive material being washed away by the blood flow. Adding an adhesive to the balloon dilatation catheter can significantly increase the adhesion of the drug to the balloon, making it less likely to be washed away by the blood flow. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0049] Figure 1 This is a contact angle test diagram of the balloon in Example 4 of the present invention;

[0050] Figure 2 This is a contact angle test diagram of the balloon in Comparative Example 2 of the present invention. DETAILED DESCRIPTION

[0051] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0052] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0053] In order to solve the problems existing in the above-mentioned related art, according to a first aspect of the present invention, a photosensitive material with a vascular repair function is provided, having a structure as shown in Formula I:

[0054]

[0055] wherein n is an integer of 1 to 6; R1 is at least one of substituted or unsubstituted C1-C10 alkylene, -C(O)-, -R3C(O)-, and -C(O)NHR4C(O)-; R3 and R4 are independently selected from substituted or unsubstituted C1-C10 alkylene;

[0056] R2 is a DNA comprising a connecting segment having a structure as shown in Formula II or Formula III, wherein the imino group connects to the R1:

[0057]

[0058] It should be noted that when R1 is -R3C(O)-, R3 is connected to NH, and C is connected to R2.

[0059] In some optional embodiments, the DNA comprises 12-16 bases;

[0060] In some optional embodiments, the molecular weight of the DNA is 4500-5300.

[0061] In some optional embodiments, the structural formula of the DNA is as follows:

[0062]

[0063] In some optional embodiments, R1, R3, and R4 are independently selected from C1-C7 alkylene.

[0064] In some optional embodiments, the substituent in the substituted C1-C10 alkylene group includes halogen, and the halogen is at least one of fluorine, chlorine, bromine, and iodine.

[0065] In some optional embodiments, the chemical structure of the photosensitive material includes:

[0066]

[0067]

[0068] It should be noted that the molecular weight of HP is 4937.23, and its specific structure is as follows:

[0069]

[0070] It should be noted that AOP-HP has a molecular weight of 5184.48 and a specific structure as follows:

[0071]

[0072] According to an embodiment of the present invention, in a second aspect, a method for preparing the photosensitive material according to the first aspect is provided, taking AOP-HP as an example, comprising method 1, method 2 and method 3, wherein:

[0073] When R1 is a substituted or unsubstituted C1-C10 alkylene group, the preparation method 1 is adopted, 1,8-naphthalimide dimer and a connecting fragment molecule containing a substitutable group are connected by a substitution reaction to obtain an intermediate 1, and the intermediate 1 is subjected to a substitution reaction with AOP-HP to obtain a photosensitive material, comprising the following steps:

[0074] (1) 1,8-Naphthaleneimide and Br-R1-Cl undergo substitution reaction to obtain intermediate 1;

[0075] (2) The intermediate 1 and AOP-HP are reacted by substitution to obtain the product.

[0076] In some optional embodiments, in step (1), the Br-R1-Cl includes at least one of 1-bromo-2-chloroethane, 1-chloro-2-bromopropane, 1-bromo-3-chloropropane, 1-bromo-3-chloro-2-methylpropane, 1-bromo-3-chlorocyclobutane, 1-bromo-4-chlorobutane, 1-bromo-4-chloropentane, 1-bromo-5-chloropentane, 1-bromo-6-chlorohexane, 1-bromo-7-chloroheptane, 1-bromo-8-chlorooctane, 1-bromo-10-chlorodecane, trans-3-bromo-1-chloro-1-propene, trans-1-bromo-4-chloro-2-butene, and 1-chloro-4-bromo-2-butanone.

[0077] In some optional embodiments, step (1) is carried out in the presence of a first organic solvent and a first organic base.

[0078] Furthermore, the first organic solvent includes at least one of acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, dimethyl sulfoxide, ethylene glycol monoethyl ether, ethylene glycol monoether, ethylene glycol dimethyl ether, and ethylene glycol diethyl ether.

[0079] Furthermore, the first organic base includes at least one of pyridine, N,N-diisopropylethylamine, triethylamine, and 1,8-diazabicycloundec-7-ene.

[0080] Furthermore, the molar ratio of the 1,8-naphthalimide dimer, the Br-R1-Cl and the first organic base is 1:20-40:30-60.

[0081] In some optional embodiments, step (1) specifically includes: dissolving 1,8-naphthaleneimide dimer in a first organic solvent to obtain a 1,8-naphthaleneimide dimer solution; then adding Br-R1-Cl and an organic base to the 1,8-naphthaleneimide dimer solution, stirring the reaction solution, and after the reaction is complete, purifying by column chromatography to obtain intermediate 1.

[0082] The reaction route is as follows:

[0083]

[0084] Wherein, R1 is a substituted or unsubstituted C1-C10 alkylene group.

[0085] In some optional embodiments, step (2) is carried out in the presence of a first organic solvent and a first inorganic base.

[0086] Furthermore, the first inorganic base includes at least one of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, and potassium bicarbonate.

[0087] Furthermore, the molar ratio of the intermediate 1, the AOP-HP and the first inorganic base is 1:10-40:30-120.

[0088] Furthermore, the reaction temperature is 50°C-120°C, and the reaction time is 12h-18h.

[0089] In some optional embodiments, step (2) specifically includes: dissolving intermediate 1 in a first organic solvent to obtain an intermediate 1 solution; dissolving a first inorganic base in deionized water to obtain an inorganic base solution; dissolving AOP-HP in deionized water to obtain an AOP-HP solution; adding the intermediate 1 solution and the inorganic base solution to the AOP-HP solution, shaking the reaction solution overnight, and after the reaction is complete, purifying the reaction solution by ethanol precipitation, ultrafiltration and desalting to obtain a structure shown in formula (I).

[0090] The reaction route is as follows:

[0091]

[0092] Wherein, R1 is a substituted or unsubstituted C1-C10 alkylene group.

[0093] Method 2, connecting an alkyl halide to the terminal amino group of AOP-HP by reacting a halogenated acyl halide with AOP-HP, and then reacting the halogenated alkyl halide with 1,8-naphthaleneimide dimer by substitution reaction, comprises the following steps:

[0094] (1) AOP-HP reacts with halogenated acyl halide to obtain intermediate 2;

[0095] (2) The intermediate 2 is reacted with 1,8-naphthaleneimide dimer to obtain;

[0096] In some optional embodiments, in step (1), the halogenated acyl halide includes at least one of chloroacetyl chloride, 2-chloropropionyl chloride, 3-chloropropionyl chloride, chlorobutyryl chloride, chlorovaleryl chloride, and chlorohexanoyl chloride.

[0097] In some optional embodiments, step (1) is carried out in the presence of a second organic solvent and a second organic base.

[0098] Furthermore, the second organic solvent includes at least one of acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, dimethyl sulfoxide, ethylene glycol monoethyl ether, ethylene glycol monoether, ethylene glycol dimethyl ether, and ethylene glycol diethyl ether.

[0099] Furthermore, the second organic base includes at least one of pyridine, N,N-diisopropylethylamine, triethylamine, and 1,8-diazabicycloundec-7-ene.

[0100] Furthermore, the molar ratio of the AOP-HP, the halogenated acyl halide and the second organic base is 1:10-40:20-80.

[0101] In some optional embodiments, step (1) specifically includes: dissolving AOP-HP in deionized water to obtain an AOP-HP solution; dissolving a halogenated acyl halide in a second organic solvent to obtain a halogenated acyl halide solution; dissolving a second organic base in a second organic solvent to obtain a second organic base solution; adding the halogenated acyl halide solution and the second organic base solution to the AOP-HP solution, shaking the reaction solution overnight, and after the reaction is complete, purifying by ethanol precipitation, ultrafiltration and desalting to obtain intermediate 2.

[0102] The reaction route is as follows:

[0103]

[0104] Wherein, R3 is a substituted or unsubstituted C1-C10 alkylene group, and X1 and X2 are each independently selected from at least one of fluorine, chlorine and bromine.

[0105] In some optional embodiments, step (2) is carried out in the presence of a third organic solvent and a third organic base.

[0106] Furthermore, the third organic solvent includes at least one of N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, dimethyl sulfoxide, ethylene glycol monoethyl ether, ethylene glycol monoether, ethylene glycol dimethyl ether, and ethylene glycol diethyl ether.

[0107] Furthermore, the third organic base includes at least one of pyridine, N,N-diisopropylethylamine, and triethylamine.

[0108] Furthermore, the molar ratio of the intermediate 2, the 1,8-naphthalimide dimer and the third organic base is 1:10-30:30-60.

[0109] Furthermore, the reaction temperature is 50°C-120°C, and the reaction time is 14h-18h.

[0110] In some optional embodiments, step (2) specifically includes: dissolving intermediate 2 in double distilled water to obtain an intermediate 2 solution; dissolving 1,8-naphthalimide dimer in a third organic solvent to obtain a 1,8-naphthalimide dimer solution; dissolving a third organic base in a third organic solvent to obtain a third organic base solution; adding the second organic base solution and the dimer solution to the intermediate 2 solution, shaking the reaction solution overnight, and after the reaction is complete, purifying the reaction solution by ethanol precipitation, ultrafiltration and desalting to obtain a structure shown in Formula I.

[0111] The reaction route is as follows:

[0112]

[0113] R3 is a substituted or unsubstituted C1-C10 alkylene group.

[0114] Method 3: AOP-HP is condensed with an amino-protected amino acid, the amino-protecting group is removed, and finally the photosensitive compound is obtained by urea formation with a 1,8-naphthalimide dimer, comprising the following steps:

[0115] (1) AOP-HP reacts with an amino acid containing an amino protecting group to obtain intermediate 3;

[0116] (2) reacting the intermediate 3 with a deprotecting agent to obtain the intermediate 4;

[0117] (3) The intermediate 4, 1,8-naphthaleneimide dimer and N,N'-succinimidyl carbonate are reacted to obtain;

[0118] In some optional embodiments, step (1) is carried out in the presence of a fourth organic solvent, a condensing agent and a fourth organic base.

[0119] Furthermore, the condensing agent includes at least one of 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholine chloride, n-propylphosphonic anhydride, 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, and O-(7-azabenzotriazol-1-yl)-bis(dimethylamino)carbonium hexafluorophosphate.

[0120] Furthermore, the fourth organic base includes at least one of N,N-diisopropylethylamine, triethylamine, pyridine, and N-methylmorpholine.

[0121] Furthermore, the fourth organic solvent includes at least one of N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, dimethyl sulfoxide, ethylene glycol monoethyl ether, ethylene glycol monoether, ethylene glycol dimethyl ether, and ethylene glycol diethyl ether.

[0122] Furthermore, the molar ratio of the DNA containing the linker fragment, the amino acid containing the amino protecting group, the condensing agent and the fourth organic base is 1:10-30:20-80:30-60.

[0123] In some optional embodiments, the amino protecting group includes at least one of 9-fluorenylmethoxycarbonyl (Fmoc), tert-butyloxycarbonyl, and benzyloxycarbonyl.

[0124] In some optional embodiments, the amino acid includes at least one of glycine, tyrosine, alanine, and 5-((((9H-fluoren-9-yl)methoxy)carbonyl)amino).

[0125] In some optional embodiments, step (1) specifically comprises: dissolving AOP-HP containing the linker fragment in double distilled water to obtain an AOP-HP solution; dissolving an amino acid containing an amino protecting group, a condensing agent, and a third organic base in a fourth organic solvent, respectively, to obtain an amino acid solution, a condensing agent solution, and a fourth organic base solution, respectively; then adding the amino acid solution, the condensing agent solution, and the fourth organic base solution to the AOP-HP solution, reacting at room temperature overnight, and after the reaction is complete, precipitating with ethanol to obtain intermediate 3.

[0126] The reaction route is as follows:

[0127]

[0128] Wherein, R4 is a substituted or unsubstituted C1-C10 alkylene group.

[0129] In some optional embodiments, in step (2), the deprotecting agent includes at least one of piperidine and trifluoroacetic acid; when the amino protecting group is 9-fluorenylmethoxycarbonyl, the deprotecting agent is piperidine; when the protecting group of the deprotecting agent is tert-butyloxycarbonyl, the deprotecting agent is trifluoroacetic acid.

[0130] In some optional embodiments, in step (2), the molar ratio of the intermediate 3 to the deprotection reagent is 1:40-80.

[0131] In some optional embodiments, step (2) specifically comprises: dissolving intermediate 3 in double distilled water to obtain an intermediate 3 solution, then adding a deprotection reagent, reacting overnight, and after the reaction is complete, precipitating with ethanol, and ultrafiltration to obtain intermediate 4;

[0132] The reaction route is as follows:

[0133]

[0134] Wherein, R4 is a substituted or unsubstituted C1-C10 alkylene group.

[0135] In some optional embodiments, step (3) is carried out in the presence of a fifth organic solvent.

[0136] Furthermore, the fifth organic solvent includes at least one of N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, dimethyl sulfoxide, ethylene glycol monoethyl ether, ethylene glycol monoether, ethylene glycol dimethyl ether, and ethylene glycol diethyl ether.

[0137] Furthermore, the molar ratio of the intermediate 4, the 1,8-naphthalimide dimer and the N,N'-succinimidyl carbonate is 1:10-30:20-40.

[0138] Furthermore, the reaction temperature is 50°C-120°C, and the reaction time is 14h-18h.

[0139] In some optional embodiments, step (3) specifically includes: dissolving intermediate 3 in double distilled water to obtain an intermediate 3 solution; dissolving N,N'-succinimidyl carbonate and 1,8-naphthalimide dimer in an organic solvent respectively to obtain an N,N'-succinimidyl carbonate solution and a 1,8-naphthalimide dimer solution respectively; then adding the N,N'-succinimidyl carbonate solution and the 1,8-naphthalimide dimer solution to the intermediate 4 solution, heating the reaction overnight, and after the reaction is completed, precipitating with ethanol, ultrafiltration, and desalting to obtain a structure shown in Formula I;

[0140] The reaction route is as follows:

[0141]

[0142] Wherein, R4 is a substituted or unsubstituted C1-C10 alkylene group.

[0143] Method 4: AOP-HP is prepared by reacting AOP-HP with N,N'-succinimidyl carbonate and 1,8-naphthaleneimide dimer to form urea;

[0144] In some optional embodiments, the reaction is carried out in the presence of a sixth organic solvent; the sixth organic solvent includes at least one of acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, dimethyl sulfoxide, ethylene glycol monoethyl ether, ethylene glycol monoether, ethylene glycol dimethyl ether, and ethylene glycol diethyl ether.

[0145] Furthermore, the molar ratio of the AOP-HP, the 1,8-naphthalimide dimer and the N,N'-succinimidyl carbonate is 1:10-40:20-60.

[0146] Furthermore, the reaction temperature is 25°C-100°C, and the reaction time is 14h-18h.

[0147] In some optional embodiments, method four specifically includes: dissolving AOP-HP in double distilled water to obtain an AOP-HP solution (10 mM), dissolving N,N'-succinimidyl carbonate in a sixth organic solvent to obtain an N,N'-succinimidyl carbonate solution (1000 mM), dissolving 1,8-naphthaleneimide dimer in a sixth organic solvent to obtain a 1,8-naphthaleneimide dimer solution (1000 mM), and then adding the N,N'-succinimidyl carbonate solution and the 1,8-naphthaleneimide dimer solution to the above-mentioned DNA solution, reacting overnight, removing impurities by ethanol precipitation, ultrafiltration, and desalting to obtain a photosensitive material.

[0148] The reaction scheme is as follows:

[0149]

[0150] According to the embodiments of the present application, in a third aspect, the present invention further provides the use of the photosensitive material with vascular repair function described in the first aspect or the photosensitive material prepared by the method described in the second aspect in the preparation of a drug for treating vascular stenosis or occlusion.

[0151] According to an embodiment of the present application, in a fourth aspect, the present application also provides a balloon dilatation catheter, comprising a balloon body; the surface of the balloon body has a coating, and the coating comprises the photosensitive material with vascular repair function described in the first aspect or the photosensitive material prepared by the method described in the second aspect.

[0152] In some optional embodiments, the method for preparing the coating includes: dissolving the photosensitive material in water to form a solution with a concentration of 0.5 mg / mL-20 mg / mL, adding 0.5 mg / mL-5 mg / mL of shellac as an adhesive, and using brushing, spraying or immersing the balloon body to form a coating on the surface of the balloon body.

[0153] After the balloon dilatation catheter provided in this application is expanded in the blood vessel, it is activated by an optical fiber of a specific wavelength (450nm), which can trigger the formation of covalent bonds between amino acids in the blood vessel wall, thereby supporting the blood vessel and preventing restenosis of the blood vessel.

[0154] It should be noted that the reaction scheme shown below, the preparation of 1,8-naphthalimide dimer refers to the literature "Solvent-Dependent Photophysics and Reactivity of Monomeric and Dimeric 4-Amino-1,8-Naphthalimides" by Kelly et al., J. Phys. Chem. A 2021, 125, 2294-2307, and includes the following steps:

[0155]

[0156] Step 1: Dissolve 4-bromo-1,8-naphthalene dicarboxylic anhydride (1 equivalent) in dimethylacetamide (5 volumes). Heat to 70°C and stir for approximately 1 hour. Then cool the mixture to room temperature and stir overnight. Filter the resulting mixture, and wash the filter cake with dimethylacetamide (1.5 volumes) and then tert-butyl methyl ether (4 volumes). The collected solid material is then dried in a vacuum oven at 65°C to constant weight, yielding purified 4-bromo-1,8-naphthalene dicarboxylic anhydride (Intermediate 5).

[0157] Step 2: To a mixture of purified 4-bromo-1,8-naphthalic anhydride (2.5 equivalents) and dimethylacetamide (8 volumes) was added N,N-diisopropylethylamine (2.5 equivalents). The mixture was then cooled to 5±5°C and slowly added dropwise with a mixture of 2,2'(ethylenedioxy)-bis(ethylamine) (1 equivalent) and dimethylacetamide (3 volumes), maintaining the reaction temperature at no more than 25°C. After the addition was complete, the resulting mixture was stirred at room temperature overnight and then at 80°C for 6 hours. The resulting mixture was filtered while hot, and the filter cake was washed with dimethylacetamide (4 times, 3 volumes each) and then with tert-butyl methyl ether (4 times, 3 volumes each). The collected material was dried in a vacuum oven at 45°C to constant weight to give 2,2'-((ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(6-bromo-1H-benzo[de]isoquinoline-1,3(2H)-dione) (i.e., intermediate 6).

[0158] Step 3: A mixture of intermediate 6 prepared in Step 2, toluene (20 volumes), and 2,2'-(ethylenedioxy)bis(ethylamine) (20 volumes) was stirred at 80°C for at least 24 hours. After cooling, stirring was continued for at least 48 hours. The resulting suspension was then filtered and washed first with toluene (3 washes, 7 volumes each) and then with acetonitrile (4 washes, 7 volumes each). The separated filter cake was dried on the filter with a stream of nitrogen and stored in the dark. The acetonitrile content of the separated material was determined by gas chromatography. The total yield of the three steps ranged from approximately 40.5% to approximately 44.5%.

[0159] The 2,2'(ethylenedioxy)-bis(ethylamine) in steps 2 and 3 can be replaced by 1,8-diamino-3,6-dioxaoctane, 1,11-diamino-3,6,9-trioxaundecane, 1,14-diamino-3,6,9,12-tetraoxatetradecane, 1,17-diamino-3,6,9,12,15-tetraoxaheptadecane or 3,6,9,12,15,18-hexaoxaeicosane-1,20-diamine.

[0160] The present invention is further described in detail below with reference to specific examples. These examples should not be construed as limiting the scope of protection claimed in the present invention.

[0161] Example 1

[0162] 51.48 mg (10 μmol) of AOP-HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM. 82.86 mg of N,N'-succinimidyl carbonate (300 μmol, 30 eq) was dissolved in 300 μL of N,N-dimethylacetamide. 160.07 mg of 1,8-naphthaleneimide dimer (200 μmol, 20 eq) was dissolved in 200 μL of N,N-dimethylacetamide; add N,N'-succinimidyl carbonate solution and 1,8-naphthaleneimide dimer solution to AOP-HP solution, react at room temperature for 16 hours and shake overnight; detect the reaction progress by liquid chromatography-mass spectrometry. After the AOP-HP is completely reacted, add 4.5mL-80°C ethanol to the reaction solution, let it stand for 2 hours, centrifuge at 4°C for 30 minutes, remove the supernatant, and vacuum dry to remove the solvent to obtain a crude product. After ultrafiltration and desalination, 50mg of photosensitive material is obtained with a yield of 83%.

[0163] The reaction route is as follows:

[0164]

[0165] Example 2

[0166] (1) 51.48 mg (10 μmol) of AOP-HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM. 38.77 mg of N,N'-diisopropylethylamine (300 μmol, 30 eq) was dissolved in 300 μL of N,N-dimethylacetamide, and 22.59 mg of chloroacetyl chloride (200 μmol, 20 eq) was dissolved in 200 μL of N,N-dimethylacetamide. The N,N'-diisopropylethylamine solution and the 1,8-naphthaleneimide dimer solution were added to the AOP-HP solution and shaken overnight at room temperature. The reaction progress was detected by liquid chromatography-mass spectrometry. After the AOP-HP reaction was completed, 4.5 mL of -80°C ethanol was added to the reaction solution. After standing for 2 h, the reaction solution was centrifuged at 4°C for 30 min, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 48 mg of intermediate 7 was obtained with a yield of 91%.

[0167] The reaction route is as follows:

[0168]

[0169] (2) Dissolve intermediate 7 (9 μmol) in 0.9 mL of double-distilled water to a concentration of 10 mM; dissolve 34.90 mg of N,N'-diisopropylethylamine (270 μmol, 30 eq) in 270 μL of N,N-dimethylacetamide; dissolve 144.07 mg of 1,8-naphthaleneimide dimer (180 μmol, 18 eq) in 180 μL of N,N-dimethylacetamide; add N,N'-succinimidyl carbonate solution and 1,8-naphthaleneimide dimer solution to the intermediate 7 solution, and shake the reaction at 90 °C for 16 h; detect the reaction progress by liquid chromatography-mass spectrometry. After all the DNA has reacted, add 4.5 mL of The mixture was added to -80°C ethanol, allowed to stand for 2 hours, and then centrifuged at 4°C for 30 minutes. The supernatant was removed and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 48.20 mg of photosensitive material was obtained with a yield of 80%.

[0170] The reaction route is as follows:

[0171]

[0172] Example 3

[0173] (1) 51.48 mg (10 μmol) of AOP-HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM. 38.77 mg of N,N'-diisopropylethylamine (300 μmol, 30 eq) was dissolved in 300 μL of N,N-dimethylacetamide, and 31.00 mg of chlorovaleryl chloride (200 μmol, 20 eq) was dissolved in 200 μL of N,N-dimethylacetamide. The N,N'-diisopropylethylamine solution and the 1,8-naphthaleneimide dimer solution were added to the AOP-HP solution and shaken overnight at room temperature. The reaction progress was detected by liquid chromatography-mass spectrometry. After the AOP-HP reaction was completed, 4.5 mL of -80°C ethanol was added to the reaction solution. After standing for 2 h, the reaction solution was centrifuged at 4°C for 30 min, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 48.3 mg of intermediate 7 was obtained with a yield of 89%.

[0174] The reaction route is as follows:

[0175]

[0176] (2) Dissolve intermediate 8 (9 μmol) in 0.9 mL of double-distilled water to a concentration of 10 mM; dissolve 34.90 mg of N,N'-diisopropylethylamine (270 μmol, 30 eq) in 270 μL of N,N-dimethylacetamide; dissolve 144.07 mg of 1,8-naphthaleneimide dimer (180 μmol, 18 eq) in 180 μL of N,N-dimethylacetamide; add N,N'-succinimidyl carbonate solution and 1,8-naphthaleneimide dimer solution to the intermediate 8 solution, and shake the reaction at 90 °C for 16 h; detect the reaction progress by liquid chromatography-mass spectrometry. After all the DNA has reacted, add 4.5 mL of The mixture was added to -80°C ethanol, allowed to stand for 2 hours, and then centrifuged at 4°C for 30 minutes. The supernatant was removed and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 48.33 mg of photosensitive material was obtained with a yield of 78%.

[0177] The reaction route is as follows:

[0178]

[0179] Example 4

[0180] (1) Dissolve 51.48 mg (10 μmol) of AOP-HP in 1 mL of double-distilled water to a concentration of 10 mM; dissolve 38.77 mg of N,N'-diisopropylethylamine (300 μmol, 30 eq) in 300 μL of N,N-dimethylacetamide, dissolve 38.34 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide, dissolve 23.02 mg of N-hydroxysuccinimide (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide, dissolve 59.46 mg of 9-fluorenylmethoxycarbonyl-glycine (200 μmol, 20 eq) in 200 μL of The above solutions were mixed and the reaction was shaken at 25°C overnight. The reaction progress was monitored by liquid chromatography-mass spectrometry. After the DNA reaction was complete, 6 mL of -80°C ethanol was added to the reaction solution. After standing for 2 hours, the reaction solution was centrifuged at 4°C for 30 minutes. The supernatant was removed and the solvent was removed by vacuum drying to obtain the crude product. After ultrafiltration and desalting, 50.81 mg of intermediate 9 was obtained, with a yield of 93%.

[0181] The reaction route is as follows:

[0182]

[0183] (2) 49.17 mg of intermediate 9 (9 μmol) was dissolved in 0.9 mL of double-distilled water to a concentration of 10 mM; 45.98 mg of piperidine (540 μmol, 60 eq) was dissolved in 600 μL of N,N-dimethylacetamide; the two solutions were mixed and shaken at room temperature for 2 hours; the reaction progress was detected by liquid chromatography-mass spectrometry. After the reaction was complete, 4.5 mL of -80°C ethanol was added to the reaction solution, and the mixture was allowed to stand for 2 hours. The mixture was centrifuged at 4°C for 30 minutes, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalination, 43.44 mg of intermediate 10 was obtained with a yield of 90%;

[0184] The reaction route is as follows:

[0185]

[0186] (3) Dissolve 43.44 mg (8.1 μmol) of intermediate 10 in 0.81 mL of double-distilled water to a concentration of 10 mM; dissolve 62.25 mg of N,N'-succinimidyl carbonate (243 μmol, 30 eq) in 243 μL of N,N-dimethylacetamide, and dissolve 129.60 mg of 1,8-naphthaleneimide dimer (162 μmol, 20 eq) in 162 μL of N,N-dimethylacetamide; add the N,N'-succinimidyl carbonate solution and the 1,8-naphthaleneimide dimer solution to the intermediate 10 solution, and shake the reaction at room temperature for 16 h; detect the reaction progress by liquid chromatography-mass spectrometry. After all the DNA has reacted, add 4.5 mL of -80℃ ethanol, after standing at -80℃ for 2h, centrifuged at 4℃ for 30min, removed the supernatant, and vacuum dried to remove the solvent to obtain a crude product. After ultrafiltration and desalting, 45.12mg of photosensitive material was obtained, with a yield of 90%.

[0187] The reaction route is as follows:

[0188]

[0189] Example 5

[0190] (1) Dissolve 51.48 mg (10 μmol) of AOP-HP in 1 mL of double-distilled water to a concentration of 10 mM; dissolve 38.77 mg of N,N'-diisopropylethylamine (300 μmol, 30 eq) in 300 μL of N,N-dimethylacetamide; dissolve 38.34 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide; dissolve 23.02 mg of N-hydroxysuccinimide (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide; and dissolve 67.88 mg of 5-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pentanoic acid (200 μmol, 20 eq) in 200 μL of The above solutions were mixed and the reaction was shaken at 25°C overnight. The reaction progress was monitored by liquid chromatography-mass spectrometry. After the DNA reaction was complete, 6 mL of -80°C ethanol was added to the reaction solution. After standing for 2 hours, the solution was centrifuged at 4°C for 30 minutes. The supernatant was removed and the solvent was removed by vacuum drying to obtain the crude product. After ultrafiltration and desalting, 51.11 mg of intermediate 11 was obtained, with a yield of 92%.

[0191] The reaction route is as follows:

[0192]

[0193] (2) 49.99 mg of intermediate 11 (9 μmol) was dissolved in 0.9 mL of double-distilled water to a concentration of 10 mM; 45.98 mg of piperidine (540 μmol, 60 eq) was dissolved in 600 μL of N,N-dimethylacetamide; the two solutions were mixed and shaken at room temperature for 2 hours; the reaction progress was detected by liquid chromatography-mass spectrometry. After the reaction was complete, 4.5 mL of -80°C ethanol was added to the reaction solution, and the mixture was allowed to stand for 2 hours. The mixture was centrifuged at 4°C for 30 minutes, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalination, 42.82 mg of intermediate 12 was obtained with a yield of 88%;

[0194] The reaction route is as follows:

[0195]

[0196] (3) Dissolve 43.78 mg (8.1 μmol) of intermediate 12 in 0.81 mL of double-distilled water to a concentration of 10 mM; dissolve 62.25 mg of N,N'-succinimidyl carbonate (243 μmol, 30 eq) in 243 μL of N,N-dimethylacetamide, and dissolve 129.60 mg of 1,8-naphthaleneimide dimer (162 μmol, 20 eq) in 162 μL of N,N-dimethylacetamide; add the N,N'-succinimidyl carbonate solution and the 1,8-naphthaleneimide dimer solution to the intermediate 12 solution, and shake the reaction at room temperature for 16 h; detect the reaction progress by liquid chromatography-mass spectrometry. After the DNA reaction is complete, add 4.5 mL of -80℃ ethanol, after standing at -80℃ for 2h, centrifuged at 4℃ for 30min, removed the supernatant, and vacuum dried to remove the solvent to obtain a crude product. After ultrafiltration and desalting, 39.37mg of photosensitive material was obtained, with a yield of 78%.

[0197] The reaction route is as follows:

[0198]

[0199] Example 6

[0200] (1) 180 mg (22.47 μmol) of 1,8-naphthaleneimide dimer was dissolved in 2 mL of N,N-dimethylacetamide; 64.45 mg (449 μmol, 20 eq) of 1-chloro-2-bromoethane and 68.21 mg (674.1 μmol, 30 eq) of triethylamine were added. After the reaction was completed by thin layer chromatography, column chromatography was performed for purification to obtain 185.18 mg of intermediate 13 with a yield of 89%;

[0201] The reaction route is as follows:

[0202]

[0203] (2) 51.48 mg (10 μmol) of AOP-HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM; 185.18 mg of intermediate 13 (200 μmol, 20 eq) was dissolved in N,N-dimethylacetamide; potassium carbonate (400 μmol, 40 eq) was dissolved in double-distilled water; the three solutions were mixed and shaken at 100 °C for 16 h. 4.5 mL of -80 °C ethanol was added to the reaction solution, and the mixture was allowed to stand at -80 °C for 2 h. The mixture was centrifuged at 4 °C for 30 min, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalination, 56 mg of photosensitive material was obtained with a yield of 93%.

[0204] The reaction route is as follows:

[0205]

[0206] Example 7

[0207] (1) 180 mg (224.7 μmol) of 1,8-naphthaleneimide dimer was dissolved in 2 mL of N,N-dimethylacetamide; 95.88 mg (4.49 mmol, 20 eq) of 1-bromo-7-chloroheptane and 68.21 mg (6.74 mmol, 30 eq) of triethylamine were added. After the reaction was completed by thin layer chromatography, column chromatography was performed for purification to obtain 212.89 mg of intermediate 14 with a yield of 89%;

[0208] The reaction route is as follows:

[0209]

[0210] (2) 51.48 mg (10 μmol) of AOP-HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM. 212.89 mg of intermediate 14 (200 μmol, 20 eq) was dissolved in N,N-dimethylacetamide. Potassium carbonate (400 μmol, 40 eq) was dissolved in double-distilled water. The three solutions were mixed and shaken at 100 °C for 16 h. 4.5 mL of -80 °C ethanol was added to the reaction solution. After standing at -80 °C for 2 h, the solution was centrifuged at 4 °C for 30 min, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalination, 51.49 mg of photosensitive material was obtained with a yield of 85%.

[0211] The reaction route is as follows:

[0212]

[0213] HP is substituted for AOP-HP at the same concentration to participate in the above reaction to obtain HP photosensitive materials, including the following embodiments:

[0214] Example 8

[0215] 49.37 mg (10 μmol) of HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM. 82.86 mg of N,N'-succinimidyl carbonate (300 μmol, 30 eq) was dissolved in 300 μL of N,N-dimethylacetamide, and 160.07 mg of 1,8-naphthaleneimide dimer (200 μmol, 20 eq) was dissolved in 200 μL of N,N-dimethylacetamide. The N,N'-succinimidyl carbonate solution and the 1,8-naphthaleneimide dimer solution were added to the HP solution and reacted at room temperature for 16 h with shaking overnight. The reaction progress was monitored by liquid chromatography-mass spectrometry. After the AOP-HP reaction was complete, 4.5 mL of The product was added to -80°C ethanol, allowed to stand for 2 hours, and then centrifuged at 4°C for 30 minutes. The supernatant was removed and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 42.12 mg of photosensitive material was obtained with a yield of 76%.

[0216] The reaction route is as follows:

[0217]

[0218] Example 9

[0219] (1) 49.37 mg (10 μmol) of HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM. 38.77 mg of N,N'-diisopropylethylamine (300 μmol, 30 eq) was dissolved in 300 μL of N,N-dimethylacetamide. 22.59 mg of chloroacetyl chloride (200 μmol, 20 eq) was dissolved in 200 μL of N,N-dimethylacetamide. The N,N'-diisopropylethylamine solution and the 1,8-naphthaleneimide dimer solution were added to the HP solution and shaken overnight at room temperature. The reaction progress was detected by liquid chromatography-mass spectrometry. After the AOP-HP reaction was completed, 4.5 mL of -80°C ethanol was added to the reaction solution. After standing for 2 h, the reaction solution was centrifuged at 4°C for 30 min, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 41.45 mg of intermediate 15 was obtained with a yield of 82%.

[0220] The reaction route is as follows:

[0221]

[0222] (2) Dissolve intermediate 15 (9 μmol) in 0.9 mL of double-distilled water to a concentration of 10 mM; dissolve 34.90 mg of N,N'-diisopropylethylamine (270 μmol, 30 eq) in 270 μL of N,N-dimethylacetamide; dissolve 144.07 mg of 1,8-naphthaleneimide dimer (180 μmol, 18 eq) in 180 μL of N,N-dimethylacetamide; add N,N'-succinimidyl carbonate solution and 1,8-naphthaleneimide dimer solution to the intermediate 11 solution, and shake the reaction at 90 °C for 16 h; detect the reaction progress by liquid chromatography-mass spectrometry. After all the DNA has reacted, add 4.5 mL of The product was added to -80°C ethanol, allowed to stand for 2 hours, and then centrifuged at 4°C for 30 minutes. The supernatant was removed and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalting, 37.43 mg of photosensitive material was obtained with a yield of 72%.

[0223] The reaction route is as follows:

[0224]

[0225] Example 10

[0226] (1) Dissolve 49.37 mg (10 μmol) of HP in 1 mL of double-distilled water to a concentration of 10 mM; dissolve 38.77 mg of N,N'-diisopropylethylamine (300 μmol, 30 eq) in 300 μL of N,N-dimethylacetamide; dissolve 38.34 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide; dissolve 23.02 mg of N-hydroxysuccinimide (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide; and dissolve 59.46 mg of 9-fluorenylmethoxycarbonyl-glycine (200 μmol, 20 eq) in 200 μL of N,N-dimethylacetamide; mix the above solutions and shake the reaction at 25°C overnight. The reaction progress was monitored by liquid chromatography-mass spectrometry. After the DNA reaction was complete, 6 mL of -80°C ethanol was added to the reaction solution. The mixture was allowed to stand for 2 h and then centrifuged at 4°C for 30 min. The supernatant was removed and the solvent was removed by vacuum drying to obtain the crude product. After ultrafiltration and desalting, 38.60 mg of intermediate 16 was obtained, with a yield of 74%.

[0227] The reaction route is as follows:

[0228]

[0229] (2) 46.94 mg of intermediate 16 (9 μmol) was dissolved in 0.9 mL of double-distilled water to a concentration of 10 mM; 45.98 mg of piperidine (540 μmol, 60 eq) was dissolved in 600 μL of N,N-dimethylacetamide; the two solutions were mixed and shaken at room temperature for 2 hours; the reaction progress was detected by liquid chromatography-mass spectrometry. After the reaction was complete, 4.5 mL of -80°C ethanol was added to the reaction solution, and the mixture was allowed to stand for 2 hours. The mixture was centrifuged at 4°C for 30 minutes, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalination, 41.89 mg of intermediate 17 was obtained with a yield of 91%;

[0230] The reaction route is as follows:

[0231]

[0232] (3) Dissolve 41.43 mg (8.1 μmol) of intermediate 17 in 0.81 mL of double-distilled water to a concentration of 10 mM; dissolve 62.25 mg of N,N'-succinimidyl carbonate (243 μmol, 30 eq) in 243 μL of N,N-dimethylacetamide, and dissolve 129.60 mg of 1,8-naphthaleneimide dimer (162 μmol, 20 eq) in 162 μL of N,N-dimethylacetamide; add the N,N'-succinimidyl carbonate solution and the 1,8-naphthaleneimide dimer solution to the intermediate 17 solution, and shake the reaction at room temperature for 16 h; monitor the reaction progress by liquid chromatography-mass spectrometry. After the DNA reaction is complete, add 4.5 mL of -80℃ ethanol, after standing at -80℃ for 2h, centrifuged at 4℃ for 30min, removed the supernatant, and vacuum dried to remove the solvent to obtain a crude product. After ultrafiltration and desalting, 41.52mg of photosensitive material was obtained with a yield of 88%.

[0233] The reaction route is as follows:

[0234]

[0235] Example 11

[0236] (1) 180 mg (22.47 μmol) of 1,8-naphthalimide dimer was dissolved in N,N-dimethylacetamide; 64.45 mg (449 μmol, 20 eq) of 1-chloro-2-bromoethane and 68.21 mg (674.1 μmol, 30 eq) of triethylamine were added. After the reaction was completed by thin layer chromatography, column chromatography was performed for purification to obtain 185.18 mg of intermediate 13 with a yield of 89%.

[0237] The reaction route is as follows:

[0238]

[0239] (2) 49.37 mg (10 μmol) of HP was dissolved in 1 mL of double-distilled water to a concentration of 10 mM; 185.18 mg of intermediate 18 (200 μmol, 20 eq) was dissolved in N,N-dimethylacetamide; potassium carbonate (400 μmol, 40 eq) was dissolved in double-distilled water; the three solutions were mixed together, the reaction solution was shaken at 100°C overnight, 4.5 mL of -80°C ethanol was added to the reaction solution, and after standing at -80°C for 2 h, the solution was centrifuged at 4°C for 30 min, the supernatant was removed, and the solvent was removed by vacuum drying to obtain a crude product. After ultrafiltration and desalination, 54 mg of photosensitive material was obtained with a yield of 93%.

[0240] The reaction route is as follows:

[0241]

[0242] Example 12

[0243] The photosensitive material and shellac prepared in Example 1 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 0.5 mg / mL. The mixed solution was evenly sprayed on the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0244] Example 13

[0245] The photosensitive material and shellac prepared in Example 2 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 0.5 mg / mL. The mixed solution was evenly sprayed on the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0246] Example 14

[0247] The photosensitive material and shellac prepared in Example 3 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 0.5 mg / mL. The mixed solution was evenly sprayed on the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0248] Example 15

[0249] The photosensitive material and shellac prepared in Example 4 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 0.5 mg / mL. The mixed solution was evenly sprayed on the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0250] Example 16

[0251] The photosensitive material and shellac prepared in Example 5 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of the shellac was 1 mg / mL. The mixed solution was evenly sprayed onto the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0252] Example 17

[0253] The photosensitive material and shellac prepared in Example 6 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 2 mg / mL. The mixed solution was evenly sprayed onto the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0254] Example 18

[0255] The photosensitive material and shellac prepared in Example 7 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of the shellac was 3 mg / mL. The mixed solution was evenly sprayed onto the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0256] Example 19

[0257] The photosensitive material and shellac prepared in Example 8 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of the shellac was 4 mg / mL. The mixed solution was evenly sprayed onto the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0258] Example 20

[0259] The photosensitive material and shellac prepared in Example 9 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of the shellac was 5 mg / mL. The mixed solution was evenly sprayed onto the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0260] Example 21

[0261] The photosensitive material and shellac prepared in Example 10 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 0.5 mg / mL. The mixed solution was evenly sprayed on the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0262] Example 22

[0263] The photosensitive material and shellac prepared in Example 11 were dissolved in double-distilled water to obtain a mixed solution. In the mixed solution, the concentration of the photosensitive material was 20 mg / mL, and the concentration of shellac was 0.5 mg / mL. The mixed solution was evenly sprayed on the balloon of the balloon dilatation catheter using an ultrasonic sprayer to form a coating.

[0264] Comparative Example 1

[0265] The only difference from Example 12 is that no coating is provided on the surface of the balloon body in this comparative example.

[0266] Comparative Example 2

[0267] The only difference from Example 14 is that 1,8-naphthaleneimide dimer is used instead of the photosensitive material in Example 3. The structure of 1,8-naphthaleneimide dimer is as follows:

[0268]

[0269] Experimental Example 1

[0270] Excess tissue around the blood vessel is stripped off, a section is cut and opened to measure the circumference of the blood vessel, denoted as a, and the initial diameter is denoted as d, where d = a / π; a balloon dilatation catheter of appropriate size is selected according to the blood vessel diameter, and the blood vessel is dilated using a balloon dilatation catheter comprising a photosensitive material coating (Example 12-Example 22, Comparative Example 2) and an ordinary balloon dilatation catheter without any coating (Comparative Example 1), respectively. After the blood vessel is pressurized to a specified pressure, it is irradiated with a 450nm optical fiber for 1 minute; after the blood vessel is irradiated, the optical fiber and balloon dilatation catheter are withdrawn, and the circumference of the dilated blood vessel is measured by cutting it open, denoted as A, and the diameter after expansion is calculated as D, where D = A / π; the blood vessel gain is calculated and denoted as X%, where X% = (Dd) / d×100%.

[0271] Table 1 Results of vasodilation experiment

[0272]

[0273] As can be seen from the table above, compared to Comparative Example 1, which did not use a photosensitive material coating, the balloon dilation catheters using a photosensitive material coating (Comparative Example 2 and Examples 12-22) all achieved a certain degree of vasodilation. Compared to Comparative Example 2, which was coated with 8-naphthaleneimide dimer, Examples 12-22 showed a more pronounced vasodilation effect. This is because, at the same dilation time, the photosensitive materials used in Examples 12-22 have excellent water solubility and can rapidly dissolve and diffuse into the vessel wall; whereas the 1,8-naphthaleneimide in Comparative Example 2 has poor water solubility and does not dissolve and diffuse well.

[0274] Experimental Example 2

[0275] The contact angle test was performed on the balloons in Example 4 and Comparative Example 2. The results are as follows: Figure 1-Figure 2 As shown, from Figure 1 It can be seen that the contact angle of the balloon prepared in Example 4 is 12.737°, and the contact angle of the balloon prepared in Comparative Example 2 is 40.660°. The smaller the contact angle, the stronger the hydrophilicity. Therefore, the balloon prepared in Example 4 is more hydrophilic than the balloon prepared in Comparative Example 2. Therefore, when the balloon dilatation catheter prepared in Example 4 is used, its photosensitive material is more likely to dissolve and diffuse into the blood vessel wall after reaching the lesion site, and can quickly exert the photo-crosslinking effect to repair the blood vessels.

[0276] Experimental Example 3

[0277] The photosensitive materials prepared in Examples 1 to 11 and the 1,8-naphthaleneimide in Comparative Example 2 were subjected to a water solubility test at 37° C. The results are shown in the table below.

[0278] Table 2 Water solubility test results

[0279]

[0280] As can be seen from the above table, the water solubility of the photosensitive material prepared in the embodiment of the present invention is >20 mg / mL, and the water solubility of 1,8-naphthaleneimide dimer is <1 mg / mL, so the water solubility of the photosensitive material prepared in the present invention is significantly higher than that of 1,8-naphthaleneimide dimer.

[0281] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A photosensitive material with vascular repair function, characterized in that: Having the structure shown in Formula I: wherein n is 1; R1 is at least one of unsubstituted C1-C10 alkylene, -C(O)-, -R3C(O)-, and -C(O)NHR4C(O)-; R3 and R4 are independently selected from unsubstituted C1-C10 alkylene; R2 is a DNA comprising a connecting segment having a structure as shown in Formula II or Formula III, wherein the imino group connects to the R1: ； The structural formula of the DNA is shown below: 。 2. The photosensitive material with vascular repair function according to claim 1, characterized in that: R1, R3, and R4 are independently selected from C1-C7 alkylene.

3. The photosensitive material with vascular repair function according to claim 2, characterized in that: The chemical structure of the photosensitive material includes: 。 4. A method for preparing the photosensitive material with vascular repair function according to any one of claims 1 to 3, characterized in that: Including Method 1, Method 2, Method 3 or Method 4, in which: When R1 is an unsubstituted C1-C10 alkylene group, the preparation method 1 comprises the following steps: (1) 1,8-naphthaleneimide dimer reacts with Br-R1-Cl to obtain intermediate a; (2) reacting the intermediate a with R2H to obtain; When R1 is -R3CO-, the preparation method 2 is adopted, comprising the following steps: (1) reacting R2H with a halogenated acyl halide to obtain intermediate b; (2) The intermediate b is reacted with 1,8-naphthalimide dimer to obtain; When R1 is -CONHR4CO-, the preparation method 3 is adopted, comprising the following steps: (1) reacting R2H with an amino acid containing an amino protecting group to obtain intermediate c; (2) reacting the intermediate c with a deprotecting agent to obtain the intermediate d; (3) The intermediate d, 1,8-naphthaleneimide dimer and N,N'-succinimidyl carbonate are reacted to obtain the product; When R1 is -CO-, the preparation method 4 is adopted, comprising the following steps: R2H, N,N'-succinimidyl carbonate and 1,8-naphthalimide dimer are reacted to form urea to obtain; The molecular structure of the 1,8-naphthalimide dimer is as follows: 。 5. The method for preparing a photosensitive material having a vascular repair function according to claim 4, characterized in that: The Br-R1-Cl comprises at least one of 1-bromo-2-chloroethane, 1-chloro-2-bromopropane, 1-bromo-3-chloropropane, 1-bromo-3-chloro-2-methylpropane, 1-bromo-3-chlorocyclobutane, 1-bromo-4-chlorobutane, 1-bromo-4-chloropentane, 1-bromo-5-chloropentane, 1-bromo-6-chlorohexane, 1-bromo-7-chloroheptane, 1-bromo-8-chlorooctane, 1-bromo-10-chlorodecane, trans-3-bromo-1-chloro-1-propene, trans-1-bromo-4-chloro-2-butene, and 1-chloro-4-bromo-2-butanone; And / or, the halogenated acyl halide comprises at least one of chloroacetyl chloride, 2-chloropropionyl chloride, 3-chloropropionyl chloride, chlorobutyryl chloride, chlorovaleryl chloride, and chlorohexanoyl chloride; And / or, the amino acid includes at least one of glycine, tyrosine, alanine, and 5-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pentanoic acid.

6. Use of the photosensitive material with vascular repair function according to any one of claims 1 to 3, or the photosensitive material prepared by the method according to claim 4 or 5, in the preparation of a drug for treating vascular stenosis or occlusion.

7. A balloon dilatation catheter, comprising a balloon body; characterized in that: The surface of the balloon body is provided with a coating, and the coating comprises an adhesive and the photosensitive material with vascular repair function according to any one of claims 1 to 3 or a photosensitive material prepared by the method according to claim 4 or 5.

8. The balloon dilatation catheter according to claim 7, characterized in that: The adhesive comprises shellac; And / or, the mass ratio of the adhesive to the photosensitive material is 0.1-1:0.1-4.

Images