Mono-substituted formic acid hydroxy aluminum phthalocyanine as well as preparation method and application thereof

Abstract

The invention discloses mono-substituted formic acid hydroxyl aluminum phthalocyanine as well as a preparation method and application thereof. The structural formula of the mono-substituted formic acid hydroxyl aluminum phthalocyanine is shown in the specification. The mono-substituted formic acid hydroxyl aluminum phthalocyanine can be used for preparing photosensitizers or photodynamic drugs or photosensitive drugs. The compound disclosed by the invention has the following characteristics that the compound exists in the form of a monomer in water, and is high in active oxygen generation capacity, low in dark toxicity and high in phototoxicity. The phototherapy index (PI) is greater than 223713, and is far higher than that of the batch phthalocyanine photosensitive drug # imgabs0 # (PI = 725). # imgabs1 #

Description

Technical Field

[0001] The invention belongs to the field of photosensitizers, and specifically relates to a monosubstituted formic acid hydroxyaluminum phthalocyanine and a preparation method and application thereof. Background Art

[0002] Phthalocyanine compounds were used as dyes in the early days. As people explored phthalocyanine, they discovered its many uses. It can be used to synthesize electrode materials, solar cell materials, photocatalytic materials, electrocatalytic materials, contrast agents in photothermal therapy, photodynamic therapy, etc.

[0003] In the past few decades, photodynamic therapy (PDT) has become a widely used treatment method for various malignant pre-lesions and malignant tumors. Photodynamic therapy is to first inject a photosensitizer into the body. After a period of time, the photosensitizer is enriched at the target, and the target is irradiated with light of a specific wavelength (for targets in the body cavity, the light source can be introduced with the help of interventional technologies such as optical fiber). The photosensitizer enriched in the target stimulates a series of photophysical and photochemical reactions under light excitation, producing reactive oxygen species, which then destroy the target (such as cancer cells and cancer tissue). Because this method has the advantage of non-invasive or minimally invasive treatment, it has many potential applications.

[0004] PDT does not show cumulative toxicity, and its activation can be controlled in space and time. The light used is adjustable and the diffusion radius of reactive oxygen species (ROS) is short, so the damage to surrounding healthy tissues can be minimized. Phthalocyanine photosensitizers have attracted widespread attention because their maximum absorption wavelength is in the red light region and they are easy to spread through human tissues. However, the biologically active phthalocyanine complexes reported so far still have some disadvantages, such as poor stability, complex synthesis routes, poor bioselectivity, and easy aggregation in aqueous solutions. Summary of the invention

[0005] Purpose of the invention: In view of the problems existing in the prior art, the present invention provides a monosubstituted formic acid hydroxyaluminum phthalocyanine, which exhibits high phototoxicity and low dark toxicity; after irradiation with low-dose light at 680nm, the dark toxicity IC 50 IC and phototoxicity 50 The ratio (phototoxicity index, PI) exceeds 223713, indicating that it has good safety; the phthalocyanine exists in the form of a monomer in water, which is conducive to the photodynamic activity in water; it is expected to be used as a photosensitizer for photodynamic therapy of cancer.

[0006] The present invention also provides a preparation method and application of the monosubstituted formic acid hydroxyaluminum phthalocyanine

[0007] Technical solution: In order to achieve the above purpose, the present invention provides a monosubstituted formic acid hydroxyaluminum phthalocyanine, the structural formula of which is as follows:

[0008]

[0009] The method for preparing the monosubstituted carboxylic acid hydroxyaluminum phthalocyanine photosensitizer of the present invention comprises the following steps:

[0010] (1) 4-nitrophthalonitrile is reacted with ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate and pentyl p-hydroxybenzoate as reactants to generate corresponding compounds (ethyl 4-(3,4-dicyanophenoxy)benzoate), (methyl 4-(3,4-dicyanophenoxy)benzoate) and (pentyl 4-(3,4-dicyanophenoxy)benzoate);

[0011] (2) 4-(3,4-dicyanophenoxy)benzoic acid ethyl ester, 4-(3,4-dicyanophenoxy)benzoic acid methyl ester or 4-(3,4-dicyanophenoxy)benzoic acid pentyl ester is cyclized with phthalonitrile to generate compound 2 and compound 3 respectively;

[0012] (3) separating the mixture of compound 2 and compound 3 to obtain compound 2;

[0013] (4) Compound 2 is hydrolyzed and deesterified to obtain monosubstituted carboxylic acid hydroxyaluminum phthalocyanine, compound 4;

[0014] The reaction formula using ethyl p-hydroxybenzoate and (ethyl 4-(3,4-dicyanophenoxy)benzoate) is as follows:

[0015]

[0016] In the reaction process, DMF refers to N,N-dimethylformamide, n-pentanol refers to n-pentanol, and DBU refers to 1,8-diazacyclo[5,4,0]undecene-7.

[0017] Wherein, in step (1), 4-nitrophthalonitrile and ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate are used as reactants, N,N-dimethylformamide is used as solvent, and the mixture is stirred at 60-80° C. for 24-48 hours in the presence of potassium carbonate and under nitrogen protection. After the reactants have reacted, they are precipitated in water to obtain the target product compound 1.

[0018] Wherein, in step (1), the molar ratio of 4-nitrophthalonitrile to ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate is 1:1-1.1, the amount of solvent used is 2-4 mL per mole of 4-nitrophthalonitrile, and the amount of potassium carbonate used is 0.93-1.1 mol per mole of 4-nitrophthalonitrile.

[0019] Wherein, in step (2), ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate and phthalonitrile are used as raw materials, n-pentanol is used as solvent, aluminum chloride is added, 1,8-diazacyclo[5,4,0]undecene-7 is used as catalyst, and the reaction is carried out at 130-140° C. for 10-12 hours under nitrogen protection to obtain compound 2 and compound 3.

[0020] Wherein, in step (2), the molar ratio of ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate to phthalonitrile and aluminum chloride is 1:9-12:3.5-5; the amount of the catalyst is 2-3 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate; and the amount of the solvent is 20-40 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate.

[0021] Wherein, in step (3), the target product compound 2 is obtained by purification by column chromatography.

[0022] Wherein, in step (4), compound 2 is used as a raw material, an alkaline reagent is added, and the reaction is carried out at 80-100° C. for 10-12 hours to obtain the target product.

[0023] Wherein, in step (4), a sodium hydroxide aqueous solution with a mass fraction of 5-20% is used, and the amount used is 0.3-0.5 mL per mg of compound 2.

[0024] As a preferred method, the preparation method of the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer comprises the following specific steps:

[0025] Step (1): The molar ratio of 4-nitrophthalonitrile to ethyl p-hydroxybenzoate is 1:1, the amount of solvent used is 2-4 mL per mol of 4-nitrophthalonitrile, and the amount of potassium carbonate used is 0.93 mol per mol of 4-nitrophthalonitrile. Under nitrogen protection, the mixture is stirred at 75° C. for 30 hours. After the reactants have reacted, they are precipitated in water to obtain the target product.

[0026] Step (2): the molar ratio of 4-(3,4-dicyanophenoxy)benzoic acid ethyl ester to phthalonitrile to aluminum chloride is 1:11:3.5-4; the amount of catalyst DBU is 2-3 mL per mol of 4-(3,4-dicyanophenoxy)benzoic acid ethyl ester; the amount of solvent n-pentanol is 20-30 mL per mol of 4-(3,4-dicyanophenoxy)benzoic acid ethyl ester, and the reaction is carried out at 140° C. for 12 hours under nitrogen protection. During the reaction, the ethyl ester in the 4-(3,4-dicyanophenoxy)benzoic acid ethyl ester participating in the cyclization will undergo an ester exchange reaction with the solvent n-pentanol, and the ethyl ester will become the pentyl ester. After the reaction is completed, the reaction solution is cooled to room temperature, and the n-pentanol is distilled off under reduced pressure. The obtained blue-black solid is refluxed with methanol (30 mL) and concentrated hydrochloric acid (2 mL) at 70°C for 2-3 h, and the filter cake is collected by hot filtration. The filter cake is washed with methanol (15 mL each time, 3 times), and the obtained solid is placed in a vacuum drying oven and dried to obtain a blue solid (a mixture of compound 2 and compound 3).

[0027] Step (3): dissolve the solid with dichloromethane, dry and mix the sample, and purify it by column chromatography. Use dichloromethane / methanol / acetic acid = 200:4:1-200:5:1 (v / v / v) as eluent to obtain monosubstituted amyl formate chloroaluminum phthalocyanine as a blue solid.

[0028] Step (4): Weigh compound 2, add 10% sodium hydroxide aqueous solution by mass, the amount of 10% sodium hydroxide aqueous solution is 0.3-0.5 mL per mg of compound 2, reflux at 100°C for 12 h, cool the reaction solution to room temperature, add concentrated hydrochloric acid to adjust the pH to 7-8, stir at room temperature for 30 min, add deionized water (30 mL), a large amount of blue solid precipitates, centrifuge to obtain the precipitate, wash with distilled water (25-30 mL each time, three times), and dry the obtained solid in a vacuum drying oven to obtain compound 4 as a blue solid.

[0029] The invention discloses an application of the monosubstituted formic acid hydroxyaluminum phthalocyanine in the preparation of photosensitizers, photodynamic drugs or photosensitizing drugs.

[0030] The monosubstituted carboxylic acid hydroxyaluminum phthalocyanine of the present invention has excellent photosensitivity and good physiological compatibility, and is suitable as a photosensitizer for photodynamic therapy of tumors.

[0031] The present invention proposes for the first time a method for synthesizing and separating monosubstituted formic acid hydroxyaluminum phthalocyanine, which has a very excellent phototherapy index PI that far exceeds that of conventional photosensitizers. The monosubstituted formic acid hydroxyaluminum phthalocyanine prepared by the present invention belongs to a photosensitizer or a photodynamic drug or a photosensitizer. The compound described in the present invention has the following characteristics: it exists in the form of a monomer in water, has a strong ability to produce active oxygen, has low dark toxicity and high phototoxicity. The phototherapy index (PI) is greater than 223713, which is much higher than that of approved phthalocyanine photosensitizers. (CAS122170-90-5)(PI=725).

[0032] When preparing and synthesizing monosubstituted formic acid hydroxyaluminum phthalocyanine in the present invention, if the carboxyl group of the phthalocyanine precursor is not protected and the reaction is directly carried out, the reaction will not be successful; at the same time, if the amount of the catalyst DBU does not reach the amount used in the present invention, the reaction will not be successful; in addition, if acetic acid is not added during the separation process, compound 2 is difficult to separate. The present invention synthesizes monosubstituted formic acid hydroxyaluminum phthalocyanine for the first time. The synthetic products of monosubstituted formic acid aluminum phthalocyanine include monosubstituted formic acid pentyl chloroaluminum phthalocyanine (compound 2) and unsubstituted aluminum phthalocyanine (compound 3). The properties of unsubstituted aluminum phthalocyanine are very similar to those of monosubstituted formic acid hydroxychloroaluminum phthalocyanine, and it is difficult to separate the target product (compound 2). The synthetic product of tetrasubstituted formic acid aluminum phthalocyanine is only the product itself, which is easy to separate. At the same time, compared with tetrasubstituted aluminum phthalocyanine such as Its phototoxic activity is 2.07 μM, which is 2315 times lower than that of the monosubstituted hydroxyaluminum phthalocyanine and is significantly lower than that of the monosubstituted phthalocyanine of the present invention.

[0033] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0034] The present invention synthesizes monosubstituted formic acid hydroxyaluminum phthalocyanine for the first time. The experimental results of the monosubstituted formic acid hydroxyaluminum phthalocyanine prepared by the present invention on in vitro cancer cells show that the dark toxicity of this type of complex is low and the phototoxicity is very high. After irradiation with low-dose light at 680nm, the dark toxicity IC 50 IC and phototoxicity 50 The phototoxicity index (PI) is more than 223713, which is much higher than the approved phthalocyanine photosensitizers. (PI=725). This compound has strong absorption in the phototherapy window (600-900nm); under photosensitivity conditions, it can effectively generate various active oxygen species. This phthalocyanine exists in the form of a monomer in water, which is conducive to the photodynamic activity in water, and is expected to be used as a photosensitizer for photodynamic therapy of cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 For the monosubstituted formic acid hydroxyaluminum phthalocyanine (10 -5 mol / L) and monosubstituted amyl formate chloroaluminum phthalocyanine (10 -5 mol / L) in water phase;

[0036] Figure 2 For the monosubstituted formic acid hydroxyaluminum phthalocyanine (10 -5 mol / L) ability to produce singlet oxygen in water phase;

[0037] Figure 3 The dark toxicity of monosubstituted formate hydroxyaluminum phthalocyanine in human bladder cancer cell T24;

[0038] Figure 4 The phototoxicity of monosubstituted formate hydroxyaluminum phthalocyanine in human bladder cancer cell T24. DETAILED DESCRIPTION

[0039] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0040] The experimental methods described in the examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0041] Example 1

[0042] Synthesis of Monosubstituted Hydroxyaluminum Phthalocyanine Formate

[0043]

[0044] The specific steps are as follows:

[0045] (1) Ethyl 4-(3,4-dicyanophenoxy)benzoate: 4-nitrophthalonitrile (2.598 g, 15.0 mmol), ethyl p-hydroxybenzoate (2.49 g, 15.0 mmol), potassium carbonate (2.0 g, 14.0 mmol) and DMF (30 mL) were added to a reaction flask in sequence. The mixture was stirred at 75°C for 30 h under N2 protection. After the reaction, the reaction solution was poured into ice water with a volume ten times that of the solvent and stirred for 30 min. A large amount of white solid was precipitated. The solid was filtered and the filter cake was washed three times with water to obtain the filter cake. The filter cake was placed in an oven and dried at 50°C for 12 h to obtain compound 1 (ethyl 4-(3,4-dicyanophenoxy)benzoate). 1H NMR (400MHz, CDCl3) δ8.17 (d, J=8.5Hz, 2H), 7.79 (d, J=8.7Hz, 1H), 7.36 (s, 1H), 7.31 (d, J=8.7Hz, 1H), 7.14 (d, J=8.5Hz, 2H), 4.43 (q, J=7.1Hz, 2H), 1.43 (t, J=7.1Hz, 3H).

[0046] (2) Monosubstituted amyl chloroaluminum phthalocyanine: Under nitrogen protection, ethyl 4-(3,4-dicyanophenoxy)benzoate (386 mg, 1.32 mmol), phthalonitrile (1.87 g, 14.59 mmol), aluminum chloride (707 mg, 5.3 mmol), and n-pentanol (40 mL) were added into a three-necked flask. The mixture was heated to 95°C under reflux and activated for 0.5 h. DBU (3 mL) was added and the mixture was rapidly heated to 140°C. The mixture was refluxed for 12 h. After the reaction, the reaction solution was cooled to room temperature, and n-pentanol was removed by distillation under reduced pressure. The obtained blue-black solid, i.e., a mixture of compound 2 and compound 3, was refluxed at 70°C for 2h with methanol (30mL) and concentrated hydrochloric acid (2mL) with a mass fraction of 37%, and the filter cake was collected by hot filtration. The filter cake was washed with methanol (15mL each time, washed 3 times), and the obtained solid was placed in a vacuum drying oven for drying to obtain a blue solid (1.5g, a mixture of monosubstituted amyl formate chloroaluminum phthalocyanine and unsubstituted chloroaluminum phthalocyanine). The solid was dissolved in 25mL of dichloromethane, dried and mixed, and purified by column chromatography, and column chromatography was performed with dichloromethane / methanol / acetic acid = 200:4:1 (v / v / v) as an eluent to obtain monosubstituted amyl formate chloroaluminum phthalocyanine as a blue solid (compound 2) (80mg, yield: 7.75%). 1 H NMR (400MHz, DMSO) δ9.80-9.58 (m, 6H), 9.24 (d, J = 2.0Hz, 1H), 8.68-8.36 (m, 7H), 8.29-8.16 (m, 3H), 7.64-7. 52(m,2H),4.38-4.31(m,2H),1.83-1.74(m,2H),1.27(dd,J=18.1,9.1Hz,4H),0.93(dd,J=11.9,4.7Hz,3H).

[0047] (3) Monosubstituted formic acid hydroxyaluminum phthalocyanine: Take monosubstituted formic acid pentyl chloroaluminum phthalocyanine (60 mg), add 10% sodium hydroxide aqueous solution (30 mL), and reflux at 100°C for 12 hours. The reaction solution was cooled to room temperature, and 37% concentrated hydrochloric acid was added to adjust the pH to 7.5. The mixture was stirred at room temperature for 30 minutes, and deionized water (30 mL) was added. A large amount of blue solid precipitated. The precipitate was centrifuged and washed three times with distilled water (25 mL each time). The obtained solid was placed in a vacuum drying oven and dried to obtain monosubstituted formic acid hydroxyaluminum phthalocyanine as a blue solid (Compound 4) (47 mg, yield: 88.35%). 1H NMR(400MHz, DMSO)δ9.78-9.58(m,7H),9.22(d,J=2.1Hz,1H),8.59-8.39(m,6H),8.28-8.16(m,3H),7.60-7.51(m,2H).HRMS(ESI,+ve)calcd.for C 39 H 21 AlN8O4 + :692.630,Found[M+H] + :693.157.

[0048] Example 2

[0049] The process is basically the same as steps (2) and (3) of Example 1, except that ethyl p-hydroxybenzoate in step (1) of Example 1 is replaced by methyl p-hydroxybenzoate, and the obtained monosubstituted formic acid hydroxyaluminum phthalocyanine has the same structure.

[0050] Example 3

[0051] The process is basically the same as steps (2) and (3) of Example 1, except that ethyl p-hydroxybenzoate in step (1) of Example 1 is replaced with pentyl p-hydroxybenzoate, and the obtained monosubstituted formic acid hydroxyaluminum phthalocyanine has the same structure.

[0052] Example 4

[0053] The steps (1), (2) and (3) of Example 1 are basically the same, except that an equal molar amount of 3-nitrophthalonitrile is used to replace the 4-nitrophthalonitrile in step (1), and the resulting phthalocyanine substituent is at the α position.

[0054]

[0055] The monosubstituted hydroxyaluminum chlorophthalocyanine synthesized in Example 1 has a side chain at the β position. According to Example 4, a monosubstituted hydroxyaluminum phthalocyanine at the α position can be synthesized. Different positions of the side chains may lead to different properties, different active oxygen generation capabilities, and changes in activity, providing more product changes.

[0056] Example 5

[0057] The absorption spectra and existence states of compound 4 and compound 2 prepared in Example 1 in water were compared. Figure 1 In an aqueous system, the concentration of 10 μM monosubstituted formic acid hydroxyaluminum phthalocyanine shows the spectral characteristics of a monomer, with a strong monomer absorption band appearing near 690nm, which is significantly stronger than the aggregate absorption band at 630nm, indicating that it mainly exists in the form of a monomer in water. Monosubstituted formic acid pentyl chloroaluminum phthalocyanine has an obvious broad peak at 630nm, which is an aggregate. Figure 1The absorption peak of monosubstituted formic acid hydroxyaluminum phthalocyanine at 690nm is higher than that at 630nm, indicating that it is mainly a monomer in water. Monosubstituted formic acid pentyl chloroaluminum phthalocyanine has a broad peak at 630nm, which is an aggregate. This proves that monosubstituted hydroxyaluminum phthalocyanine is mainly a monomer in water and is not easy to aggregate. The aggregation state affects the activity.

[0058] Example 6

[0059] like Figure 2 Example 1 Preparation of monosubstituted formic acid hydroxyaluminum phthalocyanine and monosubstituted formic acid pentyl chloroaluminum phthalocyanine in water phase singlet oxygen generation ability, 3 μL of 10 -2 mol / L of monosubstituted formic acid hydroxyaluminum phthalocyanine and 30 μL of 10 - 2 mol / L ADPA (singlet oxygen probe, anthracene-9,10-dipropionic acid CAS: 71367-28-7) was added to a cuvette containing 3 mL of distilled water and the sample was analyzed at 680 nm (25 mW / cm 2 ) red light irradiation, and ultraviolet absorption spectrum was measured every 5 minutes. The same experimental steps were used for monosubstituted amyl formate chloroaluminum phthalocyanine. The results showed that the singlet oxygen generation ability of monosubstituted amyl formate chloroaluminum phthalocyanine was significantly higher than that of monosubstituted amyl formate chloroaluminum phthalocyanine, which may be mainly due to the different aggregation states in the water phase. Monosubstituted hydroxyaluminum formate phthalocyanine is mainly monomeric in the water phase, and its singlet oxygen generation ability is stronger.

[0060] like Figure 2 The change rate of the ADPA ultraviolet absorption peak is significantly stronger for monosubstituted hydroxyaluminum formate phthalocyanine than for monosubstituted pentyl formate aluminum phthalocyanine.

[0061] Example 7

[0062] The method for preparing a photodynamic drug (i.e., a photosensitizer) using the monosubstituted formic acid hydroxyaluminum phthalocyanine prepared in Example 1 of the present invention is as follows: using dimethyl sulfoxide as a solvent, dissolving the phthalocyanine metal complex of the present invention, and preparing a blue uniform solution (i.e., a photosensitizer) with a concentration of 10 -2 mol / L, the concentration of the phthalocyanine metal complex in the photosensitizer is not higher than its saturation concentration. Antioxidants, buffers and isotonic agents can be added to the prepared solution as additives to maintain the chemical stability of the photosensitizer.

[0063] Example 8

[0064] 1 mM monosubstituted formic acid hydroxyaluminum phthalocyanine prepared in Example 1 was diluted into serum-free DMEM culture medium to prepare DMEM solutions containing phthalocyanine complexes at different concentrations. Bladder cancer (T24) cells were cultured at 10 5 / mL density was inoculated in a 96-well plate (100μL / well), and cultured in 5% CO2 at 37℃ in the dark for 24 hours. Then, different concentrations of DMEM solution containing phthalocyanine were added. After 12 hours of culture in the dark, the cells in the light experimental group were irradiated with 680nm (25mW / cm 2 ) Red light was irradiated for 10 minutes; no light operation was required for the non-irradiated group. The cell survival rate was detected by CCK8 method.

[0065] like Figure 3 , the dark toxic activity of monosubstituted hydroxyaluminum phthalocyanine against bladder cancer cells (T24). Figure 4 , the phototoxic activity of monosubstituted hydroxyaluminum phthalocyanine on bladder cancer cells (T24). The results showed that without light exposure, IC 50 When the concentration is greater than 200 μM, monosubstituted formic acid hydroxyaluminum phthalocyanine has no killing and growth inhibition effect on human bladder cancer cell T24, indicating that it has no dark toxicity; however, if irradiated with red light, monosubstituted formic acid hydroxyaluminum phthalocyanine shows significant photodynamic activity, IC 50 The PI value is greater than 223713, which is much higher than the approved phthalocyanine photosensitizers. (PI=725).

[0066]

[0067] Phthalocyanine photosensitizers reported in the literature (ACS Med. Chem. Lett. 2021, 12, 502-507) The phototoxicity is 2.07μM, and the dark toxicity is greater than 1500μΜ. High PI value photosensitizers have low toxicity to cells in the dark, so under non-illumination conditions, they have less impact on normal tissues and cells, thereby reducing side effects during treatment and improving the safety of treatment. High PI value photosensitizers have a stronger selective killing effect on cancer cells when selectively irradiating tumor tissues.

Claims

1. A monosubstituted formic acid hydroxyaluminum phthalocyanine, characterized in that: The monosubstituted formic acid hydroxyaluminum phthalocyanine structural formula is as follows:

2. A method for preparing the monosubstituted carboxylic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 1, characterized in that: The steps include: (1) 4-nitrophthalonitrile is reacted with ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate and pentyl p-hydroxybenzoate as reactants to generate corresponding compounds (ethyl 4-(3,4-dicyanophenoxy)benzoate), (methyl 4-(3,4-dicyanophenoxy)benzoate) and (pentyl 4-(3,4-dicyanophenoxy)benzoate); (2) 4-(3,4-dicyanophenoxy)benzoic acid ethyl ester, 4-(3,4-dicyanophenoxy)benzoic acid methyl ester or 4-(3,4-dicyanophenoxy)benzoic acid pentyl ester is cyclized with phthalonitrile to generate compound 2 and compound 3 respectively; (3) separating the mixture of compound 2 and compound 3 to obtain compound 2; (4) Compound 2 is hydrolyzed and deesterified to obtain monosubstituted carboxylic acid hydroxyaluminum phthalocyanine, compound 4; The reaction formula using ethyl p-hydroxybenzoate and (ethyl 4-(3,4-dicyanophenoxy)benzoate) is as follows:

3. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 2, characterized in that: In step (1), 4-nitrophthalonitrile and ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate are used as reactants, N,N-dimethylformamide is used as solvent, and the mixture is stirred at 60-80° C. for 24-48 hours in the presence of potassium carbonate and under nitrogen protection. After the reactants have reacted, they are precipitated in water to obtain the target product compound 1.

4. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 3, characterized in that: In step (1), the molar ratio of 4-nitrophthalonitrile to ethyl p-hydroxybenzoate, methyl p-hydroxybenzoate or pentyl p-hydroxybenzoate is 1:1-1.1, the amount of solvent is 2-4 mL per mole of 4-nitrophthalonitrile, and the amount of potassium carbonate is 0.93-1.1 mol per mole of 4-nitrophthalonitrile.

5. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 2, characterized in that: In step (2), ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate and phthalonitrile are used as raw materials, n-pentanol is used as solvent, aluminum chloride is added, 1,8-diazacyclo[5,4,0]undecene-7 is used as catalyst, and the reaction is carried out at 130-140° C. for 10-12 hours under nitrogen protection to obtain compound 2 and compound 3.

6. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 5, characterized in that: In step (2), the molar ratio of ethyl 4-(3,4-dicyanophenoxy)benzoate, methyl 4-(3,4-dicyanophenoxy)benzoate or pentyl 4-(3,4-dicyanophenoxy)benzoate to phthalonitrile and aluminum chloride is 1:9-12:3.5-5; the amount of the catalyst is 2-3 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate; and the amount of the solvent is 20-40 mL per mole of ethyl 4-(3,4-dicyanophenoxy)benzoate.

7. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 2, characterized in that: In step (3), the target product Compound 2 is obtained by purification by column chromatography.

8. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 2, characterized in that: In step (4), compound 2 is used as a raw material, an alkaline reagent is added, and reflux reaction is carried out at 80-100° C. for 10-12 hours to obtain the target product.

9. The method for preparing the monosubstituted formic acid hydroxyaluminum phthalocyanine photosensitizer according to claim 8, characterized in that: In step (4), a sodium hydroxide aqueous solution with a mass fraction of 5-20% is used, and the amount used is 0.3-0.5 mL per mg of compound 2.

10. Use of the monosubstituted formic acid hydroxyaluminum phthalocyanine according to claim 1 in the preparation of photosensitizers, photodynamic drugs or photosensitizing drugs.

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