Photosensitizer as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of photosensitizer preparation and biological medicine, and particularly relates to a photosensitizer and a preparation method and application thereof. The I-type photosensitizer Nile violet NV is designed and synthesized on the basis of fluorescent dye Nile red through monatomic substitution and structural modification, and the structural formula of the I-type photosensitizer Nile violet NV is shown in the formula I. The photosensitizer based on Nile red can generate O2 <.-> after illumination, and has I-type photodynamic therapy potential; the nanomaterial has a good active oxygen generation capability in tumor cells, and is beneficial to the application of tumor photodynamic therapy. The invention proves that the compound shows an excellent anti-tumor effect in mouse solid tumors and can be widely applied to the field of anti-tumor treatment; meanwhile, the I-type photosensitizer is simple in synthesis method, good in biological safety and remarkable in tumor photodynamic therapy effect, so that the I-type photosensitizer has good practical application value.

Description

Technical Field

[0001] The invention belongs to the technical field of photosensitizer preparation and biomedicine, and specifically relates to a photosensitizer and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Photodynamic therapy (PDT) is a promising treatment method with the advantages of low systemic toxicity, non-invasiveness and few side effects. During PDT, photosensitizers can produce highly toxic reactive oxygen species (ROS) under appropriate light exposure, which oxidize biological molecules in cells, mainly nucleic acids, proteins and lipids, leading to serious changes in cell signaling cascades or gene expression regulation, thereby producing cytotoxicity. According to the mechanism of ROS generation, PDT can be divided into type I and type II. Type I photochemical reactions produce free radicals through an electron transfer mechanism, including superoxide anions (O2 ·- ) and hydroxyl radicals (OH·). In the type II PDT process, molecular oxygen ( 3 O2) is converted into highly cytotoxic singlet oxygen ( 1 O2). Type I PDT is more beneficial for hypoxic tumors due to its low oxygen requirement. However, most clinically used photosensitizers rely on type II mechanisms, and the development of more effective type I photosensitizers remains challenging.

[0004] Nile Red is a well-known oxazine organic dye, which is widely recognized for its strong color and lipophilicity. At the same time, Nile Red also has many excellent photophysical and photochemical properties. Nile Red fluorescent groups have longer emission wavelengths, wider operating wavelength ranges, better photophysical and chemical stability, excellent extended conjugated structures, higher fluorescence quantum yields and molar extinction coefficients, etc. However, Nile Red dyes also have certain defects, such as strong hydrophobicity, difficult structure modification, and quantum yields that are easily affected by solvent polarity, which limit their further development and application in the field of fluorescent probes. Summary of the invention

[0005] In order to solve the above problems, the present invention provides a photosensitizer and its preparation method and application. Based on the fluorescent dye Nile red, the present invention designs and synthesizes a type I photosensitizer Nile violet NV through single atom replacement and structural modification, and applies it to the photodynamic therapy of tumors. Based on the above research results, the present invention is completed.

[0006] In order to achieve the above technical objectives, the technical solution adopted by the present invention is as follows:

[0007] The present invention provides a photosensitizer, which is a compound having a structure shown in Formula I:

[0008]

[0009] The present invention also provides a method for preparing the above-mentioned photosensitizer, the preparation method comprising:

[0010]

[0011] Preferably, the molar ratio of 2-amino-5-bromobenzenethiol to 2-chloro-1,4-naphthoquinone is 1:0.5-5, more preferably 1:1;

[0012] Preferably, the synthesis method of the compound 1 comprises: reacting 2-amino-5-bromobenzenethiol and 2-chloro-1,4-naphthoquinone in the presence of an alkaline reagent and an organic solvent; and further purifying to obtain the compound 1.

[0013] The alkaline reagent includes but is not limited to one or more of potassium hydroxide, sodium hydroxide, potassium carbonate, cesium carbonate, and triethylamine, and potassium hydroxide is more preferred;

[0014] The organic solvent is not limited to one or more of methanol, ethanol, DMF, and ethyl acetate, and methanol is more preferred. The above synthesis reaction can be carried out at room temperature;

[0015] The purification process comprises: vacuum drying the reaction solution and then purifying it by column chromatography.

[0016] Preferably, the molar ratio of the compound 1 to 1-tert-butyloxycarbonylpiperazine is 2:1-10, more preferably 2:3;

[0017] Preferably, the synthesis method of the compound Boc-NV comprises: reacting the compound 1 with 1-tert-butyloxycarbonylpiperazine in the presence of a metal catalyst, a ligand, a base and a solvent; and further purifying to obtain the compound.

[0018] The metal catalyst includes but is not limited to one or more of palladium acetate, palladium chloride, and triphenylphosphine palladium dichloride, and palladium acetate is more preferred.

[0019] The ligand is 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene.

[0020] The base includes, but is not limited to, one or more of potassium carbonate, cesium carbonate, triethylamine, and sodium carbonate, and cesium carbonate is more preferably used.

[0021] The solvent includes, but is not limited to, one or more of dioxane, toluene, water, and tetrahydrofuran, and dioxane is more preferred.

[0022] The purification process comprises: vacuum drying the reaction solution and then purifying it by column chromatography.

[0023] The synthesis method of the compound represented by formula I comprises: dissolving the compound Boc-NV in a solvent, adding a strong acid, stirring, and purifying to obtain the compound. The stirring can be performed at room temperature.

[0024] The solvent includes, but is not limited to, one or more of dichloromethane, 1,2-dichloroethane, and toluene, and dichloromethane is more preferred.

[0025] The strong acid includes, but is not limited to, one or two of trifluoroacetic acid, a methanol solution of hydrogen chloride, and a dioxane solution of hydrogen chloride, and trifluoroacetic acid is more preferred.

[0026] The purification process comprises: vacuum drying the reaction solution, extracting the obtained crude product with dichloromethane and saturated sodium bicarbonate solution, drying the organic phase with anhydrous sodium sulfate, and purifying the obtained crude product with column chromatography after vacuum drying.

[0027] The use of the above photosensitizer or the photosensitizer prepared by the above preparation method in the preparation of a photosensitizer for photodynamic therapy. Experiments have shown that its maximum absorption wavelength is around 550nm, its maximum emission wavelength is around 650nm, and it can generate active oxygen under light irradiation. In particular, as a type I photosensitizer, it has a good ability to treat hypoxic tumors, thereby effectively overcoming the dependence of traditional photosensitizers on oxygen in the hypoxic tumor environment.

[0028] Therefore, the present invention also provides the use of the above photosensitizer or the photosensitizer prepared by the above preparation method in the preparation of drugs for treating (adjuvant treating) tumors.

[0029] Meanwhile, it should be noted that tumor is used in the present invention as known to those skilled in the art, and includes benign tumors and / or malignant tumors. Benign tumors are defined as excessive proliferation of cells that cannot form aggressive, metastatic tumors in the body. Conversely, malignant tumors are defined as cells with multiple cellular abnormalities and biochemical abnormalities that can form systemic diseases (e.g., tumor metastasis in distant organs). The tumor can be a solid tumor or a blood tumor, and a solid tumor is preferred. Further, the tumor is selected from the group consisting of the following benign or malignant tumors: B-cell lymphoma, sarcoma, lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic lymphoma, anaplastic large cell lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, acute granulocytic leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic granulocytic leukemia, chronic neutrophilic leukemia, acute undifferentiated cell leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia, adult T-cell acute lymphocytic leukemia, mixed lineage leukemia, splenic marginal zone lymphoma, plasma cell myeloid leukemia, The invention relates to a type of cancer comprising the following: a tumor, plasmacytoma, extranodal marginal zone B-cell lymphoma, nodal marginal zone B-cell lymphoma, mantle cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, lymphomatoid granulomatosis, breast cancer, melanoma, brain cancer, kidney cancer, liver cancer, adrenal cancer, bladder cancer, breast cancer, lymphoma, stomach cancer, gastric tumors, esophageal cancer, ovarian cancer, colorectal cancer, prostate cancer, pancreatic cancer, lung cancer, vaginal cancer, pancreatic cancer, thyroid cancer, cervical cancer, cancer of the central nervous system (CNS), malignant glioma, myelodysplasia, glioblastoma, multiple myeloma and spinal cord sarcoma, gastrointestinal cancer, head and neck tumors, brain tumors, Hodgkin's disease, non-Hodgkin's lymphoma, or the like, or a combination thereof.

[0030] The present invention also provides a pharmaceutical composition comprising the above photosensitizer.

[0031] The pharmaceutical composition of the present invention can be administered in any manner selected from the following: oral, spray inhalation, rectal, nasal, vaginal, topical, parenteral such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal or intracranial injection or infusion, or via an explanted reservoir, wherein oral, intramuscular, intraperitoneal or intravenous administration is preferred.

[0032] The present invention also provides a pharmaceutical preparation, which comprises the above-mentioned photosensitizer and pharmaceutically acceptable excipients and / or carriers.

[0033] The above-mentioned pharmaceutical preparations can be in any pharmaceutical dosage form acceptable in pharmacy, such as tablets, hard capsules, soft capsules, pills, micropills, granules, dry suspensions, powders, oral liquids, injections, etc.

[0034] The present invention also provides a treatment system, comprising:

[0035] a) the above-mentioned photosensitizer, pharmaceutical composition or pharmaceutical preparation, and;

[0036] b) Lighting device.

[0037] Wherein, the light source emitted by the illumination device may be 400-700nm.

[0038] The present invention also provides a method for (adjuvant) treating tumors, the method comprising: administering a therapeutically effective dose of the above-mentioned photosensitizer, the above-mentioned pharmaceutical composition, the above-mentioned pharmaceutical preparation or the above-mentioned therapeutic system to a subject.

[0039] The subject refers to an animal that has been the subject of treatment, observation or experiment, preferably a mammal, and most preferably a human. "Therapeutically effective dose" refers to the amount that results in improvement of any parameter or clinical symptom. The actual dose may vary with each patient and does not necessarily refer to the total amount that eliminates all disease symptoms. It can be determined using methods known in the art and will not be described in detail here.

[0040] Beneficial technical effects of the above technical solution:

[0041] The photosensitizer based on Nile red provided by the above technical solution can produce O2 after illumination. ·- , with type I photodynamic therapy potential; the type I photosensitizer can efficiently produce ROS in solutions and cells, overcoming the shortcomings of poor photodynamic therapy effect in the hypoxic environment of tumors, and at the same time achieving strong photodynamic therapy ability for mouse solid tumors; at the same time, the above-mentioned type I photosensitizer has a simple synthesis method, good biosafety, and significant tumor photodynamic therapy effect, so it has good practical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0043] Figure 1 It is the H NMR spectrum of compound 1 in Example 1 of the present invention.

[0044] Figure 2 The NMR carbon spectrum of compound 1 in Example 1 of the present invention is

[0045] Figure 3 This is the H NMR spectrum of the compound Boc-NV in Example 1 of the present invention.

[0046] Figure 4 This is the carbon NMR spectrum of the compound Boc-NV in Example 1 of the present invention.

[0047] Figure 5 This is the H NMR spectrum of the Type I photosensitizer NV in Example 1 of the present invention.

[0048] Figure 6 This is the NMR carbon spectrum of the Type I photosensitizer NV in Example 1 of the present invention.

[0049] Figure 7 It is the ultraviolet and fluorescence spectra of the type I photosensitizer NV in the solvent in Example 2 of the present invention.

[0050] Figure 8 This is a curve diagram of the fluorescence change of the type I photosensitizer NV after interacting with DHR123 in Example 3 of the present invention.

[0051] Fig. 9 This is a graph showing the absorption change of the type I photosensitizer NV after reacting with ABDA in Example 4 of the present invention.

[0052] Fig.10 This is a graph showing the change in fluorescence intensity of the type I photosensitizer NV in Example 5 of the present invention after the action of DCFH-DA in MDA-MB-231 cells.

[0053] Fig.11 This is a graph showing the test results of the cytotoxicity of the type I photosensitizer NV on MDA-MB-231 cells under normoxic and hypoxic conditions in Example 6 of the present invention.

[0054] Fig.12 This is a diagram showing the results of photodynamic therapy of mouse tumors using the type I photosensitizer NV in Example 7 of the present invention. DETAILED DESCRIPTION

[0055] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0056] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments of the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0057] The present invention is based on the fluorescent dye Nile red, and designs and synthesizes a type I photosensitizer Nile violet NV (i.e. the compound shown in formula I) through single atom replacement and structural modification, and applies it to the photodynamic therapy of tumors.

[0058] The synthesis route of the type I photosensitizer Nile Violet NV is as follows:

[0059]

[0060] The present invention is further explained by the following examples, but they are not intended to limit the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0061] Example 1

[0062] A method for preparing a type I photosensitizer NV based on Nile red, the specific synthesis steps are as follows:

[0063] (1) Synthesis of compound 1: 2-amino-5-bromobenzenethiol (4.08 g, 20.0 mmol) was dissolved in 150 mL of methanol at room temperature, potassium hydroxide (1.23 g, 22.0 mmol) was added, and 2-chloro-1,4-naphthoquinone (4.54 g, 20 mmol) was slowly added after stirring for 30 min, and stirring was continued for 6 h at room temperature. After the reaction was completed by TLC monitoring, the reaction solution was vacuum dried, and the obtained crude product was purified by column chromatography (petroleum ether / dichloromethane, 1:1, v / v). The product was collected to obtain 3.6 g of brown solid, with a yield of 53%. 1 H-NMR (400MHz, CDCl3) δ8.88-8.77(m,1H),8.34-8.23(m,1H),7.89-7.71(m,3H),7.57(dd,J=7.2,2.0Hz,2H),6.85(s,1H). 13 C-NMR (100MHz, DMSO) δ134.39,131.91,131.66,131.18,127.27,125.98,125.68,120.89.

[0064] (2) Synthesis of compound Boc-NV: Compound 1 (410.6 mg, 1.2 mmol), 1-tert-butyloxycarbonylpiperazine (335.3 mg, 1.8 mmol), palladium acetate (13.5 mg, 0.06 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene (37.4 mg, 0.06 mmol) and cesium carbonate (586.5 mg, 1.8 mmol) were added to 12 mL of 1.4-dioxane, and the reaction solution was stirred at 100°C for 6 h. After the reaction was completed by TCL monitoring, the reaction solution was vacuum dried, and the obtained crude product was purified by column chromatography (petroleum ether / ethyl acetate, 1:1, v / v). The product was collected to obtain 467 mg of dark red solid, with a yield of 87%. 1 H-NMR (400MHz, CDCl3) δ8.72 (dd, J=7.8, 1.5Hz, 1H), 8.24 (dd, J=7.6, 1.6Hz, 1H), 7.74-7 .64(m,3H),6.69(s,1H),3.59(dd,J=6.6,3.9Hz,4H),3.31(t,J=5.3Hz,4H),1.51(s,8H). 13 C-NMR (100MHz, CDCl3) δ180.09,154.59,150.90,140.19,137.78,134.79,134.64,132.29,131.44,1 31.17,130.09,125.86,125.58,124.96,118.79,114.64,107.87,80.36,77.27,53.46,47.04,28.44.

[0065] (3) Synthesis of compound NV: Compound Boc-NV (160.0 mg, 0.36 mmol) was dissolved in 3 mL of dichloromethane, 3 mL of trifluoroacetic acid was slowly added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed by TCL monitoring, the reaction solution was vacuum dried, and the obtained crude product was extracted with 30 mL of dichloromethane and 30 mL of saturated sodium bicarbonate solution. The organic phase was dried with anhydrous sodium sulfate, and the obtained crude product was purified by column chromatography (dichloromethane / methanol, 10:1, v / v) after vacuum drying. The product was collected to obtain 467 mg of dark purple solid, with a yield of 89%. 1H-NMR (400MHz, DMSO) δ8.73(dd,J=8.1,1.3Hz,1H),8.13(dd,J=7.8,1.5Hz,1H),7.83(d,J=1.5Hz,1H), 7.80-7.72(m,2H),7.23-7.16(m,2H),6.89(s,1H),3.43(d,J=5.0Hz,4H),2.89(dd,J=6.3,3.7Hz,4H). 13 C-NMR (100MHz, DMSO) δ179.10,151.99,138.13,134.92,134.81,132.15,131.86,130 .57,130.34,126.36,125.49,124.91,118.33,114.94,107.95,47.95,45.69,40.45.

[0066] Example 2

[0067] The absorption spectrum and fluorescence emission spectrum of the photosensitizer NV synthesized in Example 1 in DMSO solution were measured using an ultraviolet-visible light analyzer and a fluorescence spectrophotometer. Figure 7 , the maximum absorption wavelength of NV is around 550nm, and the maximum emission wavelength is around 650nm.

[0068] Example 3

[0069] Dihydrorhodamine (DHR123) was used as superoxide anion (O2 ·- ) Monitoring probe detects NV producing O2 under light ·- DHR123 itself does not emit fluorescence, but can be detected by O2 ·- The photosensitizer NV and DHR123 probe were dissolved in PBS solution at a concentration of 5 μM. The mixed solution of NV and DHR123 was then exposed to light at 400-700 nm and 10 mW·cm -2 The solution was irradiated with LED light for 0, 1, 2, 3, 4, 5, 6, and 7 minutes. DHR123 without photosensitizer was used as a control, and the changes in fluorescence intensity in the solution after different illumination times were recorded. Figure 8 As shown in Figure 2, compared with the control group, the fluorescence in the mixed solution of NV and DHR123 under light conditions increased significantly with the increase of irradiation time, indicating that compound NV effectively produced O2 under light. ·- .

[0070] Example 4

[0071] 9,10-Anthracenediyl-bis(methylene)dicarboxylic acid (ABDA) was used to determine singlet oxygen ( 1O2) generation. Rose Bengal (RB) was used as a standard reference. Under dark conditions, NV ethanol solution with an absorbance of about 0.2 was mixed with ABDA ethanol solution with an absorbance of about 1.0. Using 400-700nm, 20mW·cm -2 The LED light was irradiated for 0, 5, 10, 15, 20, 25, 30 and 35 min respectively. The absorption intensity changes of ABDA probe at 380 nm after different illumination time were recorded. Fig. 9 As shown, RB can be efficiently generated under light 1 O2. However, NV did not cause a significant change in the absorbance of ABDA under light conditions, indicating that NV cannot effectively produce 1 O2.

[0072] Example 5

[0073] The ability of NV to generate ROS in MDA-MB-231 cells was detected using 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The cells were incubated with NV (0.1 μM) for 2 h and then washed. The cells were incubated with 5 μM DCFH-DA for 30 min in the dark and then illuminated with 400-700 nm, 20 mW·cm -2 The cells were irradiated with LED light for 10 min, and then collected with trypsin and analyzed by flow cytometry. Fig.10 As shown, compared with the control group without drug treatment, NV basically did not affect the fluorescence intensity of DCFH-DA under dark conditions, while 400-700nm laser irradiation could significantly enhance the fluorescence intensity of DCFH-DA, indicating that NV can effectively produce reactive oxygen in tumor cells under light irradiation.

[0074] Example 6

[0075] The CCK-8 method was used to evaluate the phototoxicity and dark toxicity of NV to MDA-MB-231 cells and 4T1 cells under normoxic (21% O2) and hypoxic conditions (2% O2). The cells were incubated with different concentrations of NV for 2 h and illuminated with 400-700 nm, 20 mW·cm -2 After irradiation with LED light for 10 min, the cells were cultured for 24 h. To determine the cell viability, the cells were incubated with CCK-8 in the dark for 4 h, and the absorbance at 450 nm was measured by an enzyme reader, and the IC 50 Value. Fig.11 As shown in Figure 2, NV has low dark toxicity but exhibits good phototoxicity under light conditions: IC 50 The value was 0.164±0.006μM, and the IC value for 4T1 cells 50The value was 0.403±0.004μM. At the same time, NV also showed excellent phototoxicity under hypoxic conditions, with an IC 50 The value was 0.303±0.015μM, and the IC value for 4T1 cells 50 The value was 0.693±0.042μM, which indicated that NV as a type I photosensitizer had good ability to treat hypoxic tumors, overcoming the dependence of traditional photosensitizers on oxygen in the hypoxic tumor environment.

[0076] Example 7

[0077] To further evaluate the therapeutic effect of NV on mouse solid tumors, 4T1 cells were subcutaneously inoculated into BALB / c mice to establish a 4T1 breast tumor-bearing mouse model, and in vivo treatment experiments were performed on 4T1 tumor-bearing mice. The mice were randomly divided into 4 groups (5 in each group): PBS group, PBS+Light group, photosensitizer NV group, and photosensitizer NV+Light group (400-700nm, 300mW·cm -2 , 5min, NV dose was 2.5mg / kg). The changes in tumor volume were recorded every 2 days. After 14 days of treatment, all mice were euthanized, and the tumors were collected and photographed. Fig.12 As shown, there was no significant change in the tumor volume of the NV group. In contrast, the tumor growth rate of the mice in the NV group after 400-700nm light irradiation was significantly slowed down, indicating that the photosensitizer NV has excellent photodynamic anti-tumor ability in vivo.

[0078] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to perform equivalent replacements on parts thereof. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention. Although the above describes the specific implementation methods of the present invention, it is not intended to limit the protection scope of the present invention. Those skilled in the art should understand that, based on the technical solution of the present invention, various modifications or deformations that can be made by those skilled in the art without creative labor are still within the protection scope of the present invention.

Claims

1. A photosensitizer, characterized in that: A compound having a structure shown in Formula I:

2. A method for preparing a photosensitizer, characterized in that: The preparation method comprises:

3. The method for preparing a photosensitizer according to claim 2, characterized in that: The molar ratio of 2-amino-5-bromobenzenethiol to 2-chloro-1,4-naphthoquinone is 1:0.5-5.

4. The method for preparing a photosensitizer according to claim 2, characterized in that: The molar ratio of compound 1 to 1-tert-butyloxycarbonylpiperazine is 2:1-10.

5. Use of the photosensitizer according to claim 1 or the photosensitizer prepared by the preparation method according to any one of claims 2 to 4 in the preparation of a photosensitizer for photodynamic therapy.

6. Use of the photosensitizer according to claim 1 or the photosensitizer prepared by the preparation method according to any one of claims 2 to 4 in the preparation of drugs for treating tumors.

7. A pharmaceutical composition, characterized in that The photosensitizer comprises the photosensitizer according to claim 1 or the photosensitizer prepared by the preparation method according to any one of claims 2 to 4.

8. A pharmaceutical preparation, characterized in that The invention comprises the photosensitizer according to claim 1 or the photosensitizer prepared by the preparation method according to any one of claims 2 to 4 and a pharmaceutically acceptable auxiliary material and / or carrier.

9. A treatment system, characterized in that: The treatment system comprises: a) the photosensitizer according to claim 1, the pharmaceutical composition according to claim 7 or the pharmaceutical preparation according to claim 8, and; b) Lighting device.

10. The treatment system according to claim 9, characterized in that: The light source emitted by the illumination device is 400-700nm.

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