A vitamin k co-crystal material for use in photodynamic therapy and a method of making the same

Abstract

The application belongs to the field of photodynamic therapy, and specifically discloses a vitamin K co-crystal material for photodynamic therapy and a preparation method thereof. The vitamin K co-crystal material takes vitamin K as an electron acceptor, and the two carbonyl groups at the para positions of the vitamin K quinoid six-membered ring make the vitamin K exhibit electron deficiency, form an organic charge transfer complex with the electron acceptor, and self-assemble to form a co-crystal, so that the absorption spectrum of the system is widened, a wider wave band of light is more effectively utilized, the photodynamic therapy response wavelength of the vitamin K is adjusted from the ultraviolet region to the visible region and the near infrared region, the problem of low penetration depth and light damage caused by photodynamic therapy using light in the ultraviolet region is avoided, and the vitamin K has excellent photodynamic performance and good application prospects in surface sterilization and disinfection, treatment of body surface infection, and directional cancer treatment based on visible light or near infrared light.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of photodynamic therapy, and particularly relates to a vitamin K co-crystal material for photodynamic therapy and a preparation method thereof. BACKGROUND

[0002] As a new type of precise treatment method with low side effects, non-invasiveness and no drug resistance, photodynamic therapy (PDT) has been applied in clinical practice as a supplement to traditional therapy. The main principle of PDT is to kill cancer cells or promote their apoptosis by generating phototoxicity after light excitation of photosensitive drugs. These photosensitive drugs are called photosensitizers, and the wavelength range of light that can excite photosensitizers is called the PDT response wavelength of photosensitizers. Photosensitizers are the core of PDT, and the development of photosensitizers with high efficiency, safety and good biocompatibility is of great significance to improve the efficacy of PDT in treating cancer. There are a large number of endogenous photosensitizers widely existing in the human body and various biological tissues. These endogenous photosensitizers have the unique advantages of excellent biocompatibility, extremely low dark toxicity and sustainable source, and therefore 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., which is a kind of nutrient necessary for the human body and plays an irreplaceable important role in maintaining various functions such as blood coagulation and calcium balance. In addition to being an important nutritional supplement, vitamin K is also an important endogenous photosensitizer. As a PDT photosensitizer, vitamin K has the advantages of high biocompatibility and low dark toxicity. However, the PDT response wavelength of vitamin K compounds is in the ultraviolet region of 200-400 nm (Chem. Rev. 2023, 123, 9720-9785.), that is, only ultraviolet light can make vitamin K compounds exhibit PDT activity. However, the penetration of ultraviolet light is poor, with a penetration depth of only about 50-150 μm, making it difficult to treat deep tissues; at the same time, ultraviolet light can easily excite other biomolecules on the light path, causing additional damage such as phototoxicity or phototoxicity (Chem. Soc. Rev. 2021, 50, 4185-4219.). Therefore, the requirement of "using ultraviolet light for excitation" limits the wider application of vitamin K compounds in PDT. Currently, the strategies for adjusting the response wavelength of photosensitizers to extend 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 (ACS Nano 2020, 14, 16840-16853.); (4) constructing composite photosensitizer materials with upconversion properties (Biomaterials 2020, 240, 119850.); (5) constructing triplet-triplet annihilation upconversion (TTA-UC) photosensitizers (Chem. Sci. 2023, 14, 13870-13878.) and the like. However, the above strategies require modification of the molecular structure of vitamin K compounds, which may change the dark toxicity and biocompatibility of vitamin K compounds; or need to be based on special optical properties such as two-photon excitation, upconversion, etc. that vitamin K compounds do not have, so they cannot be directly used to regulate the response wavelength of vitamin K compounds in PDT.

[0004] Therefore, it is necessary to develop strategies for directly regulating the response wavelength of endogenous photosensitizers such as vitamin K without chemical modification, in order to meet the demand for new and safer and more efficient PDT photosensitizers. SUMMARY

[0005] The present application 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 regulate the response wavelength, and provides a vitamin K co-crystal material for photodynamic therapy and a preparation method thereof. The vitamin K co-crystal material does not need to chemically modify the vitamin K molecule, and can adjust the photodynamic therapy response wavelength of vitamin K from the original ultraviolet region to the visible light region and the near-infrared light region, avoids the limitation that vitamin K needs to use ultraviolet light for PDT, has excellent photodynamic therapy performance, and promotes the application of vitamin K as a wide range of PDT photosensitizer.

[0006] To solve the above technical problems, the first aspect of the present application provides a vitamin K co-crystal material, comprising an electron acceptor and an electron donor, the electron acceptor is vitamin K, and the electron donor forms the vitamin K co-crystal material in combination with the electron acceptor.

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

[0008] Preferably, the vitamin K2 comprises 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 co-crystal material of the present application takes vitamin K as an electron acceptor, and forms a co-crystal with an electron donor through self-assembly. Among them: vitamin K has high biocompatibility, low dark toxicity, but needs ultraviolet light excitation, and contains a common naphthoquinone structure in the molecular structure. The two carbonyl groups at the para position on the quinoid six-membered ring of vitamin K make it exhibit electron-deficient properties, so vitamin K can be used as an electron acceptor. At the same time, the present application uses tetrathiafulvalene and pyrene containing electron-donating groups as electron donors, which are electron-rich on the pi conjugated plane. Therefore, when the electron donor is combined with the vitamin K electron acceptor, the electrons can delocalize from the donor to the acceptor. The two form an organic charge transfer (CT) complex, which widens the absorption spectrum of the system, so that a wider band of light can be more effectively utilized, achieving the effect of regulating the absorption spectrum of vitamin K. After the CT complex is arranged in a co-crystal through directional self-assembly of intermolecular non-covalent bonds, it can effectively undergo intersystem crossing to the triplet state when absorbing light excitation, and then emit energy transfer or electron transfer to produce reactive oxygen species (ROS) with O2 or the environment matrix, that is, it 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 application provides a preparation method of the above-mentioned vitamin K co-crystal material, which is a solvent evaporation method or an anti-solvent method.

[0013] As a further improvement of the above-mentioned solution, the solvent evaporation method comprises the following steps:

[0014] (1) dissolving vitamin K and electron acceptor in organic solvent respectively to obtain vitamin K solution and electron acceptor solution;

[0015] (2) mixing the vitamin K solution and electron acceptor solution to obtain a complex solution; then removing the organic solvent to obtain the vitamin K co-crystal 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 is performed by ultrasonic oscillation for 3-5 minutes.

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

[0021] As a further improvement of the above-mentioned solution, the solvent evaporation method comprises the following steps:

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

[0023] 2) mixing the vitamin K solution and electron acceptor solution to obtain a complex solution; then mixing it with water, and performing suction filtration and freeze-drying to obtain the vitamin K co-crystal 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 complex solution to water is 1:(49-99).

[0028] The third aspect of the present application provides a photosensitizer comprising the vitamin K co-crystal material described above.

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

[0030] The above technical solutions of the present application have at least the following technical effects or advantages relative to the prior art:

[0031] (1) The vitamin K co-crystal material of the present application uses vitamin K as an electron acceptor, and the two carbonyl groups at the para positions on the quinoid six-membered ring of vitamin K make it exhibit electron deficiency, form an organic charge transfer complex with an electron donor, and self-assemble to form a co-crystal, which widens the absorption spectrum of the system, thereby more effectively utilizing a wider band of light and adjusting the photodynamic therapy response wavelength of vitamin K from the ultraviolet region (200-400 nm) to the visible and near-infrared regions (400-800 nm), avoiding the problem of low penetration depth and causing photodamage caused by using light in the ultraviolet region for photodynamic therapy, and having excellent photodynamic properties.

[0032] (2) The vitamin K co-crystal material of the present application does not require modification or modification of the vitamin K molecule or strict condition control, and only needs to replace the electron donor component to achieve different regulation effects, making it suitable for wide promotion and use.

[0033] (3) The vitamin K co-crystal material of the present application is composed of small organic molecules, and has mild and simple preparation conditions and low cost, thus having good application prospects in surface sterilization and disinfection, treatment of body surface infections, and targeted cancer treatment based on visible or near-infrared light irradiation. BRIEF DESCRIPTION OF DRAWINGS

[0034] Figure 1 It is a schematic diagram of the self-assembly formation process of the vitamin K co-crystal material of the present application;

[0035] Figure 2 It is a process schematic diagram of the solvent evaporation method for preparing the vitamin K co-crystal material used in the embodiment of the present application;

[0036] Figure 3 It is a process schematic diagram of the anti-solvent method for preparing the vitamin K co-crystal material used in the embodiment of the present application;

[0037] Figure 4 It is a photograph, crystal structure, and intermolecular interaction force schematic diagram of the vitamin K co-crystal material TTF-VK3 prepared in Example 1 of the present application;

[0038] Figure 5 It is a photograph, crystal structure, and intermolecular interaction force schematic diagram of the vitamin K co-crystal material Py-VK3 prepared in Example 2 of the present application;

[0039] Figure 6The UV-Vis-NIR absorption spectra of vitamin K and the vitamin K eutectic materials (TTF-VK3 and Py-VK3) prepared in Examples 1-2 of this invention are shown.

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

[0041] Figure 8 The results of dynamic light scattering (DLS) characterization of the vitamin K co-crystal nanocrystals (TTF-VK3 and Py-VK3) suspensions prepared in Examples 3-4 of this invention;

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

[0043] Figure 10 The vitamin K eutectic nanocrystals TTF-VK3 prepared in Example 3 of this invention were subjected to 595nm LED illumination. 1 The results of O2 colorimetric probe photolysis (a) and the generation 1 Efficiency diagram of O2 (b);

[0044] Figure 11 The images (ad) and statistical sterilization rate (e) of the vitamin K co-crystal nanocrystals TTF-VK3 prepared in Example 3 of this invention killing Staphylococcus aureus under 595nm LED light irradiation are shown. Detailed Implementation

[0045] The present invention will now be described in detail with reference to embodiments to facilitate understanding of the invention by those skilled in the art. It is particularly important to note that the embodiments are merely illustrative of the invention and should not be construed as limiting the scope of protection of the invention. Non-essential improvements and adjustments made to the invention by those skilled in the art based on the above description should still fall within the scope of protection of the invention. Furthermore, all raw materials mentioned below, unless otherwise specified, are commercially available products; all process steps or preparation methods not mentioned in detail are process steps or preparation methods known to those skilled in the art.

[0046] Figure 1 This is a schematic diagram of the self-assembly formation process of the vitamin K eutectic material of the present invention, as shown below. Figure 1As shown, the present application uses Vitamin K

including Vitamin K1, Vitamin K2(MK-4), Vitamin K2(MK-7), Vitamin K3

[0047] The process schematic diagram for preparing the Vitamin K co-crystal material by the solvent evaporation method and the anti-solvent method adopted in the embodiments of the present application is shown in Figure 2 and Figure 3 respectively.

[0048] Embodiment 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 co-crystal material is formed through supramolecular self-assembly by the solvent evaporation method. The preparation method includes the following steps:

[0050] (1) 40.8 mg of TTF solid is weighed into a beaker, 5 mL of acetone is added, and ultrasonic treatment is performed at room temperature for 5 minutes to fully dissolve the TTF, obtaining a TTF acetone solution;

[0051] (2) 69.0 mg of VK3 solid is weighed into a beaker, 5 mL of acetone is added, and ultrasonic treatment is performed at room temperature for 3-5 minutes to fully dissolve the VK3, obtaining a VK3 acetone solution;

[0052] (3) The TTF and VK3 acetone solutions prepared in steps (1) and (2) are thoroughly mixed to form a dark brown organic charge transfer complex;

[0053] (4) The acetone solvent is evaporated under normal pressure or under reduced pressure using a rotary evaporator, and the intermolecular charge transfer complex formed is separated out through supramolecular assembly to form a co-crystal;

[0054] (5) The separated-out co-crystal is collected by suction filtration or by scraping it off from the inner wall of the container after the solvent is completely evaporated, obtaining a black Vitamin K co-crystal material.

[0055] Embodiment 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 co-crystal material is formed through supramolecular self-assembly by the solvent evaporation method. The preparation method includes the following steps:

[0057] (1) Take Py solid 40.4 mg into a beaker, add acetone 5 mL, ultrasonic for 5 minutes at room temperature to make Py fully dissolved, and obtain Py acetone solution;

[0058] (2) Take VK3 solid 34.5 mg into a beaker, add acetone 5 mL, ultrasonic for 3-5 minutes at room temperature to make VK3 fully dissolved, and obtain VK3 acetone solution;

[0059] (3) Mix Py and VK3 acetone solutions prepared in steps (1) and (2) to form orange-red organic charge transfer complex;

[0060] (4) Evaporate acetone solvent under normal pressure or using a rotary evaporator under reduced pressure, and the formed intermolecular charge transfer complex is precipitated by supramolecular assembly to form co-crystals;

[0061] (5) Collect the precipitated co-crystals by suction filtration or scraping from the inner wall of the container after the solvent is completely evaporated, and obtain orange vitamin K co-crystal material.

[0062] Example 3

[0063] In this example, tetra-thiafulvalene (TTF) is used as an electron donor to construct an organic charge transfer complex with vitamin K3 (VK3), and a vitamin K co-crystal material is formed by supramolecular self-assembly through an anti-solvent method. The preparation method comprises the following steps:

[0064] (1) Take TTF solid 6.0 mg into a beaker, add acetone 0.6 mL, ultrasonic for 5 minutes at room temperature to make TTF fully dissolved, and obtain TTF acetone solution;

[0065] (2) Take VK3 solid 10.0 mg into a beaker, add acetone 1 mL, ultrasonic for 3-5 minutes at room temperature to make VK3 fully dissolved, and obtain VK3 acetone solution;

[0066] (3) Mix TTF and VK3 acetone solutions prepared in steps (1) and (2) to form dark brown organic charge transfer complex;

[0067] (4) Use two injection pumps to 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 tube, and apply 20-30 W of ultrasound to the mixture using an ultrasonic transducer to form nanocrystals; collect dark vitamin K co-crystal nanocrystals in water suspension from the outlet;

[0068] (5) After suction filtration and freeze-drying of the collected suspension in step (4) to remove water, vitamin K co-crystal material is obtained.

[0069] Example 4

[0070] In this example, pyrene (Py) was used as an electron donor to construct organic charge transfer complex with vitamin K3 (VK3). Vitamin K co-crystal material was formed by supramolecular self-assembly through anti-solvent method. The preparation method comprises the following steps:

[0071] (1) Py solid 20.0 mg was weighed into a beaker, 2 mL of acetone was added, and ultrasonic was applied for 5 minutes at room temperature to make Py fully dissolved, obtaining Py acetone solution;

[0072] (2) VK3 solid 19.5 mg was weighed into a beaker, 2 mL of acetone was added, and ultrasonic was applied for 3-5 minutes at room temperature to make VK3 fully dissolved, obtaining VK3 acetone solution;

[0073] (3) The Py and VK3 acetone solutions prepared in steps (1) and (2) were mixed thoroughly to form dark brown organic charge transfer complex;

[0074] (4) The organic charge transfer complex obtained in step (3) and water were mixed at a volume ratio of 1: (49-99) through a three-way tube at a total flow rate of 10-20 mL / min using two syringe pumps, and 20-30 W of ultrasound was applied using an ultrasonic transducer to assist the rapid mixing to form nanocrystals; a dark vitamin K co-crystal nanocrystal suspension in water was collected from the outlet;

[0075] (5) After the suspension collected in step (4) was subjected to suction filtration and freeze-drying to remove water, vitamin K co-crystal material was obtained.

[0076] Performance characterization and testing

[0077] 1. Macroscopic morphology and crystal structure

[0078] The macroscopic morphology and crystal structure of the vitamin K co-crystal materials prepared in Examples 1-2 were observed, and the results are shown in Figures 4-5

[0079] As can be seen from Figures 4-5 , the Py-VK3 co-crystal is an orange-yellow square-shaped crystal, and the TTF-VK3 co-crystal is a dark brown flaky crystal. X-ray diffraction (XRD) was used to characterize the co-crystal crystals obtained by solvent evaporation, and the crystal structures of the two co-crystals were obtained. As shown in Figure 5 , Py and VK3 form Py-VK3 co-crystal at a molecular ratio of 1:1. There are rich intermolecular interactions inside the co-crystal. First, in the same stacking column, the electron-rich Py centroid and the electron-deficient quinone ring center of VK3 are arranged in an overlapping manner with a spacing of ​(①) and (②) staggered arrangement. Secondly, there are abundant C-H···O hydrogen bonds in the Py-VK3 molecule. There are two C-H···O hydrogen bonds in the adjacent but non-parallel packing column, including the distance from H on Py to C=O bond of VK3 (③) with the bond angle of 133.96°; and the distance from H on the benzene ring of VK3 to C=O bond of another molecule of VK3 (④) with the bond angle of 156.51°. There are two C-H···O hydrogen bonds in the adjacent and parallel packing column, including the distance from H on Py to C=O bond of VK3 (⑤) with the bond angle of 143.12°; and the distance from H on the benzene ring of VK3 to C=O bond of another molecule of VK3 (⑥) with the bond angle of 118.89°. As shown in Figure 4 , in TTF-VK3, TTF and VK3 molecules form a composition eutectic with a ratio of 1:2. In the same packing column, the electron-rich C=C double bond center of TTF is arranged in an overlapping manner with the electron-deficient quinone ring center of VK3 and the electron-rich benzene ring center of another molecule of VK3. The distance between the C=C double bond center of TTF and the quinone ring center of VK3 is (①), while the distance between the quinone ring centers of two adjacent molecules of VK3 and the benzene ring center of another molecule of VK3 is (②). In addition, two strong C-H···O hydrogen bonds are observed in the TTF-VK3 eutectic. The distance between the C=O bond of VK3 and one H of TTF in the adjacent two packing columns is (③) with the bond angle of 122.55°; and the distance between the C=O bond of VK3 and the hydrogen at position 3 of the quinone ring of VK3 in another packing column is (④) with the bond angle of 163.15°. The analysis of the crystal structure confirms that there are abundant intermolecular weak forces in the two eutectics, which are beneficial to the averaging of electron clouds, making the vertical transition energy levels of the eutectics lower and denser.

[0080] 2. Absorption spectrum

[0081] The ultraviolet-visible-near infrared absorption spectrum of vitamin K and the vitamin K eutectic material prepared in Examples 1-2 was observed, and the results are shown in Figure 6 .

[0082] As can be seen from Figure 6 , the absorption spectrum range of the vitamin K eutectic prepared in Examples 1-2 with TTF as the electron donor can reach 300-1200 nm (as shown in Figure 6c), the vitamin K co-crystal with Py as the electron donor can absorb light in the range of 300-600 nm (e.g. Figure 6 b), while VK3 only absorbs light before 370 nm and has no absorption after 370 nm (e.g. Figure 6 a). This is because when the above-mentioned electron donor is combined with the vitamin K electron acceptor, the electron can be delocalized from the donor to the acceptor. The two form a charge transfer (CT) state, which in turn widens the absorption spectrum of the system, thereby enabling more efficient use of a wider band of light. When such a CT complex is arranged in a co-crystal through intermolecular non-covalent forces, the co-crystal also has this property of 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 chemistry theoretical calculations were performed on pyrene, TTF, VK3 and the vitamin K co-crystal materials prepared in Examples 1-2, and the results are shown in Figure 7 .

[0085] As can be seen from Figure 7 , the HOMO-LUMO energy gap of the formed vitamin K co-crystal relative to its monomer is narrowed. For example, the energy gap of the frontier orbital of Py is 3.45 eV, that of TTF is 3.23 eV, and that of VK3 is 3.71 eV, while the HOMO-LUMO energy gap of the Py-VK3 and TTF-VK3 co-crystals is only 2.29 eV and 1.33 eV, respectively (e.g. Figure 7 a), which is consistent with the absorption cutoff of the two vitamin K co-crystals, indicating that the absorption wavelength of the co-crystal is red-shifted. In addition, the vertical transition energy level of the two vitamin K co-crystals is also lower and narrower relative to their monomers, indicating that the absorption spectrum of the co-crystal is widened (e.g. Figure 7 b), which is consistent with the results observed in Figure 7 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] Dynamic light scattering (DLS) characterization was performed on the vitamin K co-crystal nanocrystal suspensions (TTF-Vk3 NPs suspension and Py-Vk3 NPs suspension) prepared in Examples 3-4, and the results are shown in Figure 8 b and Figure 8 a, respectively.

[0088] FromFigure 8 The particle size distribution diagrams of vitamin K cocrystal nanocrystals in the two suspensions shown in the figure indicate that the vitamin K cocrystal nanocrystals prepared by the antisolvent method have a particle size mainly distributed between 300-400 nm in the suspension, which is nanoscale and relatively uniform. This suggests that the nanocrystal suspensions prepared by this method facilitate the preparation of vitamin K cocrystal materials into various liquid formulations, which helps improve the bioavailability of vitamin K cocrystal materials and facilitates their use in photodynamic therapy.

[0089] 5. X-ray powder diffraction characterization

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

[0091] from Figure 9 It can be seen that the vitamin K eutectic nanocrystals prepared by the antisolvent method are only slightly different from those prepared by the solvent evaporation method in terms of crystal size and growth orientation, while the crystal structure, that is, the specific arrangement or packing form of the molecules, remains unchanged.

[0092] 6. Evaluation of photodynamic therapy activity

[0093] The photodynamic therapeutic activity of the vitamin K cocrystal nanocrystals prepared in Example 3 under visible light irradiation was evaluated, and the results are as follows: Figure 10 As shown, where: Figure 10 a represents the curve showing the change in concentration of the vitamin K co-crystal nanocrystals and their monomers against the indocyanine green colorimetric probe over time under 530 nm illumination. Figure 10 b represents the production of vitamin K cocrystal nanocrystals derived from the indocyanine green light irradiation experiment. 1 The efficiency of O2 production is related to its monomer production. 1 Comparison of the sum of O2 efficiencies (Coformers).

[0094] Figure 10 This demonstrates the generation of singlet oxygen in vitamin K eutectic nanocrystals using TTF as an electron donor under irradiation with a 30W LED lamp at a wavelength of 595nm. 1 The situation regarding O2). From... Figure 10 As can be seen, the TTF-VK3 eutectic can be effectively generated under 595nm orange-red light irradiation. 1O2, with an efficiency 4.9 times that of the sum of coformers, demonstrates that the vitamin K cocrystal material prepared in this invention can indeed produce [coformation] under visible light irradiation. 1 O2 effectively modulates the photodynamic therapy response wavelength of vitamin K from the ultraviolet region to the visible region, realizing visible light-driven photodynamic therapy.

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

[0096] The photodynamic therapy and bactericidal activity of the vitamin K cocrystal nanocrystals prepared in Example 3 under visible light irradiation was evaluated, and the results are as follows: Figure 11 As shown.

[0097] Figure 11 This demonstrates the photodynamic therapy and killing of Staphylococcus aureus using vitamin K cocrystal nanocrystals with TTF as the electron donor, under irradiation with a 100W LED lamp at a wavelength of 595nm. From... Figure 11 As can be seen, *Staphylococcus aureus* grew well in the control group (ControlDark), and 100W 595nm light irradiation had no significant effect on its growth. Only after adding TTF-VK3 cocrystal to the culture medium and applying light irradiation did the number of *Staphylococcus aureus* bacteria decrease significantly, with a statistically significant inhibition rate of 96%. This demonstrates that the vitamin K cocrystal material prepared according to this invention can indeed achieve photodynamic therapy under visible light irradiation. Therefore, it has excellent application prospects in surface sterilization and disinfection based on visible or near-infrared light irradiation, treatment of skin infections, and targeted cancer therapy.

[0098] For those skilled in the art, several simple deductions or substitutions can be made without departing from the inventive concept, without requiring creative effort. Therefore, any simple improvements made to this invention by those skilled in the art based on the disclosure of this invention should be within the scope of protection of this invention. The above embodiments are preferred embodiments of this invention, and all processes similar to this invention and equivalent changes should fall within the scope of protection of this invention.

Claims

1. A vitamin K eutectic material, characterized in that, The material includes an electron acceptor and an electron donor, wherein the electron acceptor is vitamin K and the electron donor is tetrathiofulvalene, and the electron acceptor and the electron donor are combined to form the vitamin K eutectic material; the vitamin K eutectic material has an X-ray diffraction pattern as shown in Figure 9 of the specification.

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 molar ratio of the electron donor to the electron acceptor is 1:(1-2).

4. A method for preparing a vitamin K eutectic material as described in any one of claims 1-3, characterized in that, The preparation method is either solvent evaporation or antisolvent method.

5. The method for preparing the vitamin K eutectic material according to claim 4, characterized in that, The solvent evaporation method includes the following steps: (1) Dissolve vitamin K and electron donor in organic solvents respectively to obtain vitamin K solution and electron donor solution; (2) The vitamin K solution and the electron donor solution are mixed to obtain a composite solution; then the organic solvent is removed to obtain the vitamin K eutectic material.

6. The method for preparing the vitamin K eutectic material according to claim 5, 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 donor solution is 0.04-0.05 mol / mL.

7. The method for preparing the vitamin K eutectic material according to claim 4, characterized in that, The antisolvent method includes the following steps: 1) Dissolve vitamin K and electron donor separately in organic solvents to obtain vitamin K solution and electron donor solution; 2) The vitamin K solution and the electron donor solution are mixed to obtain a composite solution; then the composite solution is mixed with water, filtered and freeze-dried to obtain the vitamin K eutectic material.

8. A photosensitizer, characterized in that, Includes the vitamin K eutectic material as described in any one of claims 1-3.

9. The use of the photosensitizer according to claim 8 in the preparation of a photodynamic antibacterial drug, wherein the photodynamic antibacterial strain is Staphylococcus aureus.

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