Vitamin K eutectic material for photodynamic therapy and preparation method thereof

Abstract

The invention belongs to the field of photodynamic therapy, and particularly discloses a vitamin K eutectic material for photodynamic therapy and a preparation method of the vitamin K eutectic material. The vitamin K eutectic material takes vitamin K as an electron acceptor, two para-position carbonyl groups on a quinonoid six-membered ring of the vitamin K enable the vitamin K to show an electron-deficient property, and the vitamin K and the electron acceptor form an organic charge transfer compound and are self-assembled to form eutectic, so that the absorption spectrum of a system is widened, light with a wider wave band is more effectively utilized, and the utilization rate of the light is improved. The photodynamic therapy response wavelength of the vitamin K is adjusted from an ultraviolet region to a visible region and a near-infrared region, so that the problem of light damage caused by low penetration depth due to photodynamic therapy by using light in the ultraviolet region is avoided, and the vitamin K has excellent photodynamic performance and can be applied to the field of photodynamic therapy. The method has a good application prospect in surface sterilization and disinfection based on visible light or near-infrared light illumination, body surface infection treatment and directional cancer treatment.

Description

Technical Field

[0001] The present invention belongs to the field of photodynamic therapy, and in particular relates to a vitamin K eutectic material for photodynamic therapy and a preparation method thereof. Background Art

[0002] Photodynamic therapy (PDT) is a new type of precision treatment with low side effects, non-invasiveness, and no drug resistance. It has been used clinically as a supplement to traditional therapies. The main principle of PDT is that light excites photosensitizers to produce phototoxicity, thereby killing cancer cells or inducing their apoptosis. These photosensitizers are called photosensitizers, and the range of light wavelengths that can excite photosensitizers is called the PDT response wavelength of the photosensitizer. Photosensitizers are the core of PDT. The development of efficient, safe, and biocompatible photosensitizers is of great significance to improving the efficacy of PDT in treating cancer. There are many endogenous photosensitizers in the human body and even in various biological tissues. These endogenous photosensitizers have the unique advantages of excellent biocompatibility, extremely low dark toxicity, and sustainable sources. Therefore, they are gradually recognized and valued as a new type of PDT photosensitizer.

[0003] Vitamin K is a general term for a class of compounds including vitamin K1, K2 (MK-4), K2 (MK-7), K3, etc. It is a type of nutrient necessary for the human body and plays an irreplaceable and important role in maintaining human coagulation, calcium balance and other functions. In addition to being an important nutritional supplement, vitamin K is also an important endogenous photosensitizer. As a PDT photosensitizer, vitamin K has the significant advantages of high biocompatibility and low dark toxicity. However, the PDT response wavelength of vitamin K compounds is located in the ultraviolet region of 200-400nm (Chem.Rev.2023,123,9720-9785.), that is, only ultraviolet light can make vitamin K compounds exhibit PDT activity. However, ultraviolet light has poor penetration, with a penetration depth of only about 50-150μm, making it difficult to treat deep tissues; at the same time, ultraviolet light can easily excite other biological molecules in the light path, causing additional damage such as photosensitivity or phototoxicity (Chem.Soc.Rev.2021,50,4185-4219.). Therefore, the "need to use ultraviolet light excitation" limits the wider application of vitamin K compounds in PDT. The current strategies for adjusting the response wavelength of photosensitizers to extend it to the visible region or even the near-infrared region mainly include: (1) Modifying the molecular structure to increase conjugation or introduce -π conjugated auxochromes (J.Am.Chem.Soc.2018,140,7343-7346); (2) Introducing excited state intermolecular charge transfer (Angew.Chem.Int.Ed.2020,59,8957-8962.); (3) Developing photosensitizers capable of two-photon excitation (ACSNano 2020, 14, 16840-16853.); (4) constructing composite photosensitizers with upconversion properties (Biomaterials 2020, 240, 119850.); (5) constructing triplet-triplet annihilation upconversion (TTA-UC) photosensitizers (Chem. Sci. 2023, 14, 13870-13878.), etc. However, the above strategies require the modification of the molecular structure of vitamin K compounds, which may change the dark toxicity and biocompatibility of vitamin K compounds; or they need to be based on special photophysical properties that vitamin K compounds do not have, such as two-photon excitation and upconversion, so they cannot be directly used to regulate the PDT response wavelength of vitamin K compounds.

[0004] Therefore, it is very necessary to develop strategies to directly regulate the response wavelength of endogenous photosensitizers such as vitamin K without chemical modification to meet people's demand for safer and more efficient new PDT photosensitizers. Summary of the invention

[0005] The present invention aims at the technical problem that the PDT light response wavelength of vitamin K is in the ultraviolet region and it is difficult to directly adjust its response wavelength, and proposes a vitamin K eutectic material for photodynamic therapy and a preparation method thereof. The vitamin K eutectic material can adjust its photodynamic therapy response wavelength from the original ultraviolet region to the visible light region and the near-infrared region without chemically modifying the vitamin K molecule, avoiding the limitation that vitamin K needs to use ultraviolet light for PDT, having excellent photodynamic therapy performance, and promoting the application of vitamin K as a wide range of PDT photosensitizers.

[0006] In order to solve the above technical problems, the first aspect of the present invention provides a vitamin K eutectic material, comprising an electron acceptor and an electron donor, wherein the electron acceptor is vitamin K, which is combined with the electron donor to form the vitamin K eutectic material.

[0007] Preferably, the vitamin K includes at least one of vitamin K1, vitamin K2 and vitamin K3.

[0008] Preferably, the vitamin K2 includes vitamin K2 (MK-4) and / or vitamin K2 (MK-7).

[0009] Preferably, the electron donor comprises tetrathiafulvalene (TTF) and / or pyrene (Py).

[0010] Specifically, the vitamin K eutectic material of the present invention uses vitamin K as an electron acceptor and forms a eutectic with an electron donor by self-assembly. Among them: vitamin K has high biocompatibility and low dark toxicity, but requires ultraviolet light excitation, and its molecular structure contains a common naphthoquinone structure. The two para-carbonyl groups on the six-membered ring of the vitamin K quinone make it exhibit electron-deficient properties, so vitamin K can be used as an electron acceptor. At the same time, the present invention uses tetrathiafulvalene and pyrene containing electron-pushing groups as electron donors, and their π-conjugated planes are electron-rich. Therefore, when the electron donor is combined with the vitamin K electron acceptor, the electrons can be delocalized from the donor to the acceptor. The two form an organic charge transfer (CT) complex, which in turn broadens the absorption spectrum of the system, thereby being able to more effectively utilize light in a wider band to achieve the effect of regulating the absorption spectrum of vitamin K. After this CT complex is self-assembled and arranged to form a eutectic through intermolecular non-covalent bond forces, it can effectively undergo intersystem crossing to reach the triplet state when absorbing light excitation, and then emit energy transfer or electron transfer with O2 or the environmental matrix to produce reactive oxygen species (ROS), which can effectively perform PDT.

[0011] Preferably, the molar ratio of the electron donor to the electron acceptor is 1:(1-2).

[0012] The second aspect of the present invention provides a method for preparing the above-mentioned vitamin K eutectic material, which is a solvent volatilization method or an anti-solvent method.

[0013] As a further improvement of the above scheme, the solvent volatilization method comprises the following steps:

[0014] (1) Dissolving vitamin K and an electron acceptor in an organic solvent to obtain a vitamin K solution and an electron acceptor solution;

[0015] (2) Mixing the vitamin K solution and the electron acceptor solution to obtain a composite solution; then removing the organic solvent to obtain the vitamin K eutectic material.

[0016] Preferably, in step (1), the molar concentration of the vitamin K solution is 0.04-0.08 mol / mL.

[0017] Preferably, in step (1), the molar concentration of the electron acceptor solution is 0.04-0.05 mol / mL.

[0018] Preferably, in step (1), the organic solvent comprises acetone.

[0019] Preferably, in step (2), the mixing method is ultrasonic shaking for 3-5 minutes.

[0020] Preferably, in step (2), the organic solvent is volatilized at normal pressure or under reduced pressure using a rotary evaporator.

[0021] As a further improvement of the above scheme, the anti-solvent method comprises the following steps:

[0022] 1) Dissolving vitamin K and an electron acceptor in an organic solvent respectively to obtain a vitamin K solution and an electron acceptor solution;

[0023] 2) Mixing the vitamin K solution and the electron acceptor solution to obtain a composite solution; then mixing the composite solution with water, filtering, and freeze-drying to obtain the vitamin K eutectic material.

[0024] Preferably, in step 1), the molar concentration of the vitamin K solution is 0.04-0.08 mol / mL.

[0025] Preferably, in step 1), the molar concentration of the electron acceptor solution is 0.04-0.05 mol / mL.

[0026] Preferably, in step 1), the organic solvent comprises acetone.

[0027] Preferably, in step 2), the volume ratio of the composite solution to water is 1:(49-99).

[0028] The third aspect of the present invention provides a photosensitizer, comprising the above-mentioned vitamin K eutectic material.

[0029] The fourth aspect of the present invention provides the use of the above-mentioned photosensitizer in the preparation of photodynamic antibacterial or photodynamic anticancer drugs.

[0030] Compared with the prior art, the above technical solution of the present invention has at least the following technical effects or advantages:

[0031] (1) The vitamin K eutectic material of the present invention uses vitamin K as an electron acceptor. The two para-carbonyl groups on the vitamin K quinone six-membered ring make it exhibit electron-deficient properties. It forms an organic charge transfer complex with an electron donor and self-assembles to form a eutectic, which broadens the absorption spectrum of the system, thereby more effectively utilizing light of a wider wavelength band, and adjusting the photodynamic therapy response wavelength of vitamin K from the ultraviolet light region (200-400nm) to the visible light region and the near-infrared light region (400-800nm), thereby avoiding the problems of low penetration depth and photodamage caused by using light in the ultraviolet light region for photodynamic therapy, and having excellent photodynamic performance.

[0032] (2) The vitamin K eutectic material of the present invention does not require modification of the vitamin K molecule or strict condition control. Different regulatory effects can be achieved simply by replacing the electron donor component, and is suitable for wide promotion and use.

[0033] (3) The vitamin K eutectic material of the present invention is composed of organic small molecules, and the preparation conditions are mild and simple, and the cost is low. Therefore, it has good application prospects in surface sterilization and disinfection based on visible light or near-infrared light, treatment of body surface infection and targeted cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a schematic diagram of the self-assembly formation process of the vitamin K eutectic material of the present invention;

[0035] Figure 2 A schematic diagram of the process for preparing vitamin K eutectic material by solvent evaporation method adopted in an embodiment of the present invention;

[0036] Figure 3 A schematic diagram of the process for preparing vitamin K eutectic material by the anti-solvent method adopted in an embodiment of the present invention;

[0037] Figure 4 The photo, crystal structure and schematic diagram of intermolecular interaction force of the vitamin K eutectic material TTF-VK3 prepared in Example 1 of the present invention;

[0038] Figure 5 The photo, crystal structure and schematic diagram of intermolecular interaction force of the vitamin K eutectic material Py-VK3 prepared in Example 2 of the present invention;

[0039] Figure 6The UV-visible-near infrared absorption spectra of vitamin K and the vitamin K eutectic materials (TTF-VK3 and Py-VK3) prepared in Examples 1-2 of the present invention;

[0040] Figure 7 HOMO-LUMO energy levels and energy gaps (a) and vertical transition energy levels (b) obtained by quantum chemical calculation for Pyrene, TTF, VK3 and vitamin K eutectic materials (TTF-VK3 and Py-VK3) prepared in Examples 1-2 of the present invention;

[0041] Figure 8 The dynamic light scattering (DLS) characterization results of the vitamin K cocrystal nanocrystal (TTF-VK3 and Py-VK3) suspension prepared in Examples 3-4 of the present invention;

[0042] Fig. 9 The powder X-ray diffraction (PXRD) characterization results of the vitamin K cocrystal nanocrystals (TTF-VK3 and Py-VK3) prepared in Examples 3-4 of the present invention;

[0043] Fig.10 The vitamin K eutectic nanocrystal TTF-VK3 prepared in Example 3 of the present invention was used under 595nm LED light. 1 The results of O2 colorimetric probe photolysis (a) and the production 1 Efficiency diagram of O2 (b);

[0044] Fig.11 The photos (ad) and statistical sterilization rate (e) of the vitamin K cocrystal nanocrystal TTF-VK3 prepared in Example 3 of the present invention killing Staphylococcus aureus under 595nm LED light. DETAILED DESCRIPTION

[0045] The present invention is described in detail below in conjunction with the examples, so that the technical personnel of the relevant technical field can understand the present invention. It is necessary to point out here that the examples are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. The non-essential improvements and adjustments made to the present invention by the skilled person in the relevant field according to the above invention content should still belong to the scope of protection of the present invention. At the same time, the raw materials mentioned below that are not described in detail are all commercially available products; the process steps or preparation methods that are not mentioned in detail are all process steps or preparation methods known to those skilled in the art.

[0046] Figure 1 Schematic diagram of the self-assembly formation process of the vitamin K eutectic material of the present invention, Figure 1As shown, the present invention uses vitamin K with ultraviolet light response [including Vitamin K1, Vitamin K2 (MK-4), Vitamin K2 (MK-7), Vitamin K3] as an electron acceptor, constructs a CT complex with an electron donor, and regulates the light response wavelength of vitamin K through supramolecular self-assembly to form a vitamin K eutectic with visible light response and suitable for photodynamic therapy.

[0047] The process schematic diagrams of preparing vitamin K eutectic material by solvent evaporation method and anti-solvent method used in the embodiment of the present invention are as follows: Figure 2 and Figure 3 shown.

[0048] Example 1

[0049] In this embodiment, tetrathiafulvalene (TTF) is used as an electron donor to construct an organic charge transfer complex with vitamin K3 (VK3), and a vitamin K eutectic material is formed by supramolecular self-assembly using a solvent evaporation method. The preparation method includes the following steps:

[0050] (1) Weigh 40.8 mg of TTF solid and place it in a beaker, add 5 mL of acetone, and sonicate at room temperature for 5 minutes to fully dissolve TTF to obtain an acetone solution of TTF;

[0051] (2) Weigh 69.0 mg of VK3 solid and place it in a beaker, add 5 mL of acetone, and sonicate at room temperature for 3-5 minutes to fully dissolve VK3. An acetone solution of VK3 is obtained;

[0052] (3) fully mixing the TTF prepared in step (1) and step (2) with the acetone solution of VK3 to form a dark brown organic charge transfer complex;

[0053] (4) volatilizing the acetone solvent at normal pressure or under reduced pressure using a rotary evaporator, and the formed intermolecular charge transfer complex precipitates through supramolecular assembly to form a cocrystal;

[0054] (5) Collect the precipitated eutectic by suction filtration or by scraping it off the inner wall of the container after the solvent is completely evaporated to obtain a black vitamin K eutectic material.

[0055] Example 2

[0056] In this embodiment, pyrene (Py) is used as an electron donor to construct an organic charge transfer complex with vitamin K3 (VK3), and a vitamin K eutectic material is formed by supramolecular self-assembly using a solvent evaporation method. The preparation method includes the following steps:

[0057] (1) Weigh 40.4 mg of Py solid and place it in a beaker, add 5 mL of acetone, and perform sonication at room temperature for 5 minutes to fully dissolve Py to obtain an acetone solution of Py;

[0058] (2) Weigh 34.5 mg of VK3 solid and place it in a beaker, add 5 mL of acetone, and sonicate at room temperature for 3-5 minutes to fully dissolve VK3. An acetone solution of VK3 is obtained;

[0059] (3) fully mixing the Py prepared in step (1) and step (2) with the acetone solution of VK3 to form an orange-red organic charge transfer complex;

[0060] (4) volatilizing the acetone solvent at normal pressure or under reduced pressure using a rotary evaporator, and the formed intermolecular charge transfer complex precipitates through supramolecular assembly to form a cocrystal;

[0061] (5) Collect the precipitated eutectic by suction filtration or by scraping it off the inner wall of the container after the solvent is completely evaporated to obtain an orange vitamin K eutectic material.

[0062] Example 3

[0063] In this embodiment, tetrathiafulvalene (TTF) is used as an electron donor to construct an organic charge transfer complex with vitamin K3 (VK3), and an antisolvent method is used to form a vitamin K eutectic material through supramolecular self-assembly. The preparation method includes the following steps:

[0064] (1) Weigh 6.0 mg of TTF solid and place it in a beaker, add 0.6 mL of acetone, and perform sonication at room temperature for 5 minutes to fully dissolve TTF to obtain an acetone solution of TTF;

[0065] (2) Weigh 10.0 mg of VK3 solid and place it in a beaker, add 1 mL of acetone, and sonicate at room temperature for 3-5 minutes to fully dissolve VK3. An acetone solution of VK3 is obtained;

[0066] (3) fully mixing the TTF prepared in step (1) and step (2) with the acetone solution of VK3 to form a dark brown organic charge transfer complex;

[0067] (4) using two syringe pumps to rapidly mix the organic charge transfer complex obtained in step (3) with water at a volume ratio of 1:(49-99) at a total flow rate of 10-20 mL / min through a three-way pipe, and simultaneously using an ultrasonic transducer to apply 20-30 W of ultrasound to assist in rapid mixing to form nanocrystals; collecting a dark-colored suspension of vitamin K cocrystal nanocrystals in water from the outlet;

[0068] (5) The suspension collected in step (4) is filtered and freeze-dried to remove water to obtain a vitamin K eutectic material.

[0069] Example 4

[0070] In this embodiment, pyrene (Py) is used as an electron donor to construct an organic charge transfer complex with vitamin K3 (VK3), and an antisolvent method is used to form a vitamin K eutectic material through supramolecular self-assembly. The preparation method includes the following steps:

[0071] (1) Weigh 20.0 mg of Py solid and place it in a beaker, add 2 mL of acetone, and perform sonication at room temperature for 5 minutes to fully dissolve Py to obtain an acetone solution of Py;

[0072] (2) Weigh 19.5 mg of VK3 solid and place it in a beaker, add 2 mL of acetone, and sonicate at room temperature for 3-5 minutes to fully dissolve VK3. An acetone solution of VK3 is obtained;

[0073] (3) fully mixing the Py prepared in step (1) and step (2) with the acetone solution of VK3 to form a dark brown organic charge transfer complex;

[0074] (4) using two syringe pumps to rapidly mix the organic charge transfer complex obtained in step (3) with water at a volume ratio of 1:(49-99) at a total flow rate of 10-20 mL / min through a three-way pipe, and simultaneously using an ultrasonic transducer to apply 20-30 W of ultrasound to assist in rapid mixing to form nanocrystals; collecting a dark-colored suspension of vitamin K cocrystal nanocrystals in water from the outlet;

[0075] (5) The suspension collected in step (4) is filtered and freeze-dried to remove water to obtain a vitamin K eutectic material.

[0076] Performance Characterization and Testing

[0077] 1. Macroscopic morphology and crystal structure

[0078] The macroscopic morphology and crystal structure of the vitamin K eutectic materials prepared in Examples 1-2 were observed, and the results were as follows: Figure 4-5 shown.

[0079] from Figure 4-5 It can be seen that the Py-VK3 eutectic is an orange-yellow square flaky crystal, while the TTF-VK3 is a dark brown flaky crystal. The eutectic crystals obtained by the solvent evaporation method were characterized by X-ray diffraction (XRD), and the crystal structures of the two eutectics were obtained. Figure 5 As shown in Figure 1, Py and VK3 form a Py-VK3 cocrystal with a molecular ratio of 1:1. There are abundant intermolecular interactions inside the cocrystal. First, in the same stacking column, the electron-rich Py mass center and the electron-deficient quinone ring center of VK3 overlap and are separated by (marked as ①) and (marked as ②) staggered arrangement. Secondly, there are abundant CH···O hydrogen bonds in the Py-VK3 molecule. There are two types of CH···O hydrogen bonds in adjacent but non-parallel stacking columns, including the H on Py to the C=O bond of VK3, with a distance of (marked as ③), the bond angle is 133.96°; the distance from the H on the benzene ring of VK3 to the C=O bond of another molecule of VK3 is (marked as ④), the bond angle is 156.51°. There are two types of CH···O hydrogen bonds between adjacent and parallel stacking columns, including the one from the H on Py to the C=O bond of VK3, with a distance of (marked as ⑤), the bond angle is 143.12°; the distance from the H on the benzene ring of VK3 to the C=O bond of another molecule of VK3 is (marked as ⑥), the bond angle is 118.89°. Figure 4 As shown in Figure 1, in TTF-VK3, TTF and VK3 molecules form a eutectic in a ratio of 1:2. In the same stacking column, the electron-rich C=C double bond center of TTF overlaps with the electron-deficient quinone ring center of VK3 and the electron-rich benzene ring center of another molecule VK3. The distance between the C=C double bond center and the quinone ring center of VK3 is (marked as ①), and the distance between the quinone ring center of two adjacent VK3 molecules and the benzene ring center of another VK3 molecule is (Marked as ②). In addition, two strong CH···O hydrogen bonds were observed in the TTF-VK3 eutectic. Between two adjacent stacking columns, the distance between the C=O bond of VK3 and one H of TTF is (marked as ③), the bond angle is 122.55°; the distance between the C=O bond of VK3 and the hydrogen at position 3 of the quinone ring of VK3 in another stacking column is (marked as ④), the bond angle is 163.15°. The analytical structure of the crystal confirmed the existence of abundant intermolecular weak forces in the two eutectics, which is conducive to the averaging of the electron cloud, making the vertical transition energy level of the eutectic lower and more dense.

[0080] 2. Absorption spectrum

[0081] The UV-visible-near infrared absorption spectra of vitamin K and the vitamin K eutectic material prepared in Example 1-2 were observed, and the results were as follows: Figure 6 shown.

[0082] from Figure 6 It can be seen that the absorption spectrum range of the vitamin K eutectic prepared in Examples 1-2 with TTF as the electron donor can reach 300-1200nm (e.g. Figure 6c) The absorption spectrum of vitamin K eutectic with Py as electron donor can reach 300-600nm (e.g. Figure 6 b), while VK3 only absorbs before 370nm and has no absorption after 370nm (e.g. Figure 6 a). This is because when the above electron donor is combined with the vitamin K electron acceptor, the electrons can be delocalized from the donor to the acceptor. The two form a charge transfer (CT) state, which in turn broadens the absorption spectrum of the system, thereby being able to more effectively utilize light in a wider band. When this CT complex is oriented to form a co-crystal through intermolecular non-covalent bond forces, the co-crystal also has the property of this wide absorption spectrum. Therefore, the vitamin K co-crystal formed by vitamin K and the electron donor can effectively absorb and utilize visible light.

[0083] 3.HOMO-LUMO energy level, energy gap and vertical transition energy level

[0084] Quantum chemical theoretical calculations were performed on Pyrene, TTF, VK3 and the vitamin K eutectic materials prepared in Examples 1-2. The results are as follows: Figure 7 shown.

[0085] from Figure 7 It can be seen that the HOMO-LUMO energy gap of the vitamin K cocrystal formed is narrower than that of its monomer. For example, the frontier orbital energy gap of Py is 3.45eV, TTF is 3.23eV, and VK3 is 3.71eV, while the HOMO-LUMO energy gaps of Py-VK3 and TTF-VK3 cocrystals are only 2.29eV and 1.33eV, respectively (e.g. Figure 7 a), which is consistent with the absorption cutoff of the two vitamin K cocrystals, indicating that the absorption wavelength is red-shifted after the cocrystal is formed. In addition, the vertical transition energy level of the two vitamin K cocrystals is lower and narrower than that of the monomers, indicating that the absorption spectrum becomes wider after the cocrystal is formed (e.g. Figure 7 b), with Figure 7 This is consistent with the results observed in a, further confirming that the charge transfer interaction between vitamin K and the electron donor component can effectively regulate the absorption spectrum of the material.

[0086] 4. Dynamic Light Scattering Characterization

[0087] The vitamin K cocrystal nanocrystal suspensions (TTF-Vk3 NPs suspension and Py-Vk3 NPs suspension) prepared in Examples 3-4 were characterized by dynamic light scattering (DLS). The results were as follows: Figure 8 b and Figure 8 As shown in a.

[0088] from Figure 8 The particle size distribution diagram of the vitamin K eutectic nanocrystals in the two suspensions shown in the figure shows that the particle size of the vitamin K eutectic nanocrystals prepared by the anti-solvent method in the suspension is mainly distributed between 300-400nm, the particle size is nanometer-level, and the particle size distribution is relatively uniform. This indicates that the nanocrystal suspension prepared by this preparation method is convenient for the preparation of vitamin K eutectic materials into various liquid preparations, which helps to improve the bioavailability of vitamin K eutectic materials and facilitates photodynamic therapy.

[0089] 5. X-ray powder diffraction characterization

[0090] The vitamin K co-crystal nanocrystals (TTF-Vk3 and Py-Vk3) prepared in Examples 3-4 were characterized by X-ray powder diffraction (PXRD). The results were as follows: Fig. 9 b and Fig. 9 As shown in a, Intensity in the figure represents the intensity of the peak, Experiment represents the PXRD spectrum of the eutectic powder prepared in Example 3-4, and Simulation represents the PXRD spectrum of the theoretical simulation of the crystal structure of the eutectic obtained by the solvent evaporation method.

[0091] from Fig. 9 It can be seen that the vitamin K eutectic nanocrystals prepared by the anti-solvent method are only slightly different from the eutectic nanocrystals prepared by the solvent evaporation method in crystal size and growth orientation, while the crystal structure, that is, the specific arrangement or stacking form of the molecules, has not changed.

[0092] 6. Evaluation of Photodynamic Therapy Activity

[0093] The photodynamic therapy activity of the vitamin K co-crystal nanocrystals prepared in Example 3 was evaluated under visible light. The results are as follows: Fig.10 As shown, where: Fig.10 a is the curve of the concentration of indocyanine green colorimetric probe of vitamin K cocrystal nanocrystal and its monomer under 530nm light as a function of light exposure time. Fig.10 b is the vitamin K eutectic nanocrystal yield calculated from the indocyanine green illumination experiment 1 O2 efficiency and its monomer production 1 Comparison of the efficiency of O2 and (Coformers).

[0094] Fig.10 It was demonstrated that under the irradiation of LED light with a power of 30W and a wavelength of 595nm, vitamin K cocrystal nanocrystals with TTF as electron donor produced singlet oxygen ( 1 O2). Fig.10 b It can be seen that TTF-VK3 eutectic can effectively produce under 595nm orange-red light irradiation (595nm irradiation) 1O2, its efficiency is 4.9 times that of the sum of co-crystal monomers (Coformers). This shows that the vitamin K eutectic material prepared by the present invention can indeed produce 1 O2, that is, effectively adjusting the photodynamic therapy response wavelength of vitamin K from the ultraviolet region to the visible region, thereby realizing visible light-driven photodynamic therapy.

[0095] 7. Evaluation of bactericidal activity of photodynamic therapy

[0096] The photodynamic therapy bactericidal activity of the vitamin K eutectic nanocrystals prepared in Example 3 was evaluated under visible light. The results are as follows: Fig.11 shown.

[0097] Fig.11 The results show that under the irradiation of LED light with a power of 100W and a wavelength of 595nm, the photodynamic therapy of vitamin K cocrystal nanocrystals with TTF as electron donor can kill Staphylococcus aureus. Fig.11 It can be seen that the Staphylococcus aureus in the light-proof blank group (ControlDark) grows well, and the 100W 595nm light has no significant effect on the growth of Staphylococcus aureus. Only after adding TTF-VK3 eutectic to the culture medium and applying light, the number of Staphylococcus aureus (Number of Bacterial) is significantly reduced, and the bactericidal rate (Inhibition Rate) can reach 96% after statistics. It shows that the vitamin K eutectic material prepared according to the present invention can indeed achieve photodynamic therapy under visible light irradiation. Therefore, it has a good application prospect in surface sterilization and disinfection based on visible light or near-infrared light, treatment of body surface infection and targeted cancer treatment.

[0098] For ordinary technicians in the technical field to which the present invention belongs, several simple deductions or substitutions can be made without departing from the concept of the present invention, without having to go through creative labor. Therefore, simple improvements made to the present invention by those skilled in the art based on the disclosure of the present invention should be within the protection scope of the present invention. The above embodiments are preferred embodiments of the present invention, and all processes similar to the present invention and equivalent changes made should belong to the protection scope of the present invention.

Claims

1. A vitamin K eutectic material, characterized in that: It comprises an electron acceptor and an electron donor, wherein the electron acceptor is vitamin K, and is combined with the electron donor to form the vitamin K eutectic material.

2. The vitamin K eutectic material according to claim 1, characterized in that The vitamin K includes at least one of vitamin K1, vitamin K2, and vitamin K3.

3. The vitamin K eutectic material according to claim 1, characterized in that The electron donor includes tetrathiafulvalene and / or pyrene.

4. The vitamin K eutectic material according to claim 1, characterized in that The molar ratio of the electron donor to the electron acceptor is 1:(1-2).

5. A method for preparing the vitamin K eutectic material according to any one of claims 1 to 4, characterized in that: The preparation method is a solvent volatilization method or an anti-solvent method.

6. The method for preparing the vitamin K eutectic material according to claim 5, characterized in that: The solvent volatilization method comprises the following steps: (1) Dissolving vitamin K and an electron acceptor in an organic solvent to obtain a vitamin K solution and an electron acceptor solution; (2) mixing the vitamin K solution and the electron acceptor solution to obtain a composite solution; then removing the organic solvent to obtain the vitamin K eutectic material.

7. The method for preparing the vitamin K eutectic material according to claim 6, characterized in that: The molar concentration of the vitamin K solution is 0.04-0.08 mol / mL; and / or the molar concentration of the electron acceptor solution is 0.04-0.05 mol / mL.

8. The method for preparing the vitamin K eutectic material according to claim 5, characterized in that: The anti-solvent method comprises the following steps: 1) Dissolving vitamin K and an electron acceptor in an organic solvent to obtain a vitamin K solution and an electron acceptor solution, respectively; 2) mixing the vitamin K solution and the electron acceptor solution to obtain a composite solution; then mixing the composite solution with water, filtering, and freeze-drying to obtain the vitamin K eutectic material.

9. A photosensitizer, characterized in that The method comprises the vitamin K eutectic material according to any one of claims 1 to 4.

10. Use of the photosensitizer according to claim 9 in the preparation of photodynamic antibacterial or photodynamic anticancer drugs.

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