Device and method for preparing photosensitizer

Abstract

The invention relates to the field of material preparation, in particular to a photosensitizer preparation device and a photosensitizer preparation method. The device comprises a reaction cavity, a passivation cavity and a drying cavity which are sequentially connected, a storage chamber I and a storage chamber II are arranged above the reaction cavity, a storage chamber III is arranged below the reaction cavity, and a storage chamber IV is arranged above the passivation cavity; each storage chamber is provided with a solution spray gun, and temperature control layers are arranged on the outer layers of the reaction cavity, the passivation cavity and the drying cavity; a temperature control sleeve is arranged on the outer layer of each storage chamber; the reaction cavity, the passivation cavity and the drying cavity are all provided with temperature sensors; a ventilation gate I and a ventilation port are arranged at the left end of the reaction cavity, a ventilation gate II is arranged between the reaction cavity and the passivation cavity, a ventilation gate III is arranged between the passivation cavity and the drying cavity, and an outlet of the drying cavity communicates with the collecting cavity. And the collecting cavity, the reaction cavity and the passivation cavity are all provided with pressure controllers. The preparation method disclosed by the invention integrates preparation, passivation modification, drying and collection to obtain a solid nano-granular photosensitizer, and the solid nano-granular photosensitizer is directly prepared into a spray after being prepared in a medical place and is administrated through a respiratory tract for photodynamic therapy.

Description

Technical Field

[0001] The invention relates to the field of material preparation, and in particular to a device and a method for preparing a photosensitizer. Background Art

[0002] The preparation process of photosensitizers used in photodynamic therapy is complicated and usually requires multi-step solution reactions in a chemical laboratory. It also requires a variety of equipment to assist in controlling the reaction conditions. Therefore, it can generally only be carried out in professional laboratories and requires high professional technical requirements. The colloidal solution photosensitizers prepared by this solution method are mostly treated by intravenous injection, which is prone to damage to normal tissues, causing side effects such as bone marrow suppression and gastrointestinal reactions. In addition, the colloidal solution photosensitizers are not easy to preserve and cannot be prepared and used immediately before use. During long-term transportation and storage, clusters and precipitation are easily formed, which directly affects the efficacy of the photosensitizers. The molecular composition of photosensitizers is diverse. During treatment, it is often necessary to quickly adjust the photosensitizer component structure according to the condition to cooperate with the treatment plan. The feedback laboratory preparation process consumes a lot of time, resulting in delays in the condition. If we can get rid of the limitations of laboratory sites and professional technicians and directly prepare solid photosensitizers at the treatment site, on the one hand, we can optimize the components and functions in time according to the treatment needs, and prepare the photosensitizers directly on site, saving the preparation time of the photosensitizers and no need for professional technicians to operate; on the other hand, without affecting the treatment effect, solid photosensitizers are easier to use and store, and can be directly prepared into spray preparations for administration through respiratory contact, avoiding the side effects of intravenous injection. In addition, the quantum dots used in traditional photosensitizers often contain components such as organic polymers and Cd-based quantum dots, which are not easy to degrade in the body and pose potential toxic threats. There is an urgent need for a quantum dot material that can be designed as a completely non-toxic component. At present, there is no device that can be prepared under conventional indoor conditions, with a simple method and controllable conditions, and can be compatible with multiple component controls and directly prepare solid photosensitizers. Summary of the invention

[0003] The invention provides a novel device for preparing photosensitizer, and provides a method for preparing photosensitizer by using the device.

[0004] The photosensitizer prepared by the present invention may have an inorganic semiconductor quantum dot (such as II-VI and III-V main group semiconductor quantum dots) as its core, or may have AMX3, (RNH3)2A n-1 MX 3n+1 、R(NH3)2A n-1 MX 3n+1 、A(1)A(2) n–1 MX 3n+1, A2M(I)M(III)X6, A2M(IV)X6, A2M(I)M(II)X5, A3M(III)2X9, A4BM(II)M(III)2X 12 、A4M(III)M(V)X 12 , A4M(I)M(III)X8, A2B(I)B(III)MX8, and similar (C9NH 20 )6[Pb3Br 12 ] and (C9NH 20 )9[ZnBr4]2[Pb3Br 11 ] and other forms of perovskite quantum dots, including the above series of hybrid quantum dots in the form of component mixing and element doping. A, A(1), A(2) are monovalent cations, which can be inorganic elements or smaller organic groups; R is a larger organic cation; M is a metal cation; X is a halogen anion; NH3 is an ammonium ion.

[0005] In order to achieve the above-mentioned invention object, the present invention adopts the following technical solutions:

[0006] The invention provides a photosensitizer preparation device, comprising a reaction chamber, a passivation chamber, and a drying chamber connected in sequence; a storage chamber I and a storage chamber II are arranged above the reaction chamber, a storage chamber III is arranged below the reaction chamber, and a storage chamber IV is arranged above the passivation chamber; solution spray guns I, II, and IV are arranged below the storage chambers I, II, and IV, respectively, and a solution spray gun III is arranged above the storage chamber III; the nozzles of the solution spray guns I, II, and III are passed into the reaction chamber, and the nozzle of the solution spray gun IV is passed into the passivation chamber; the outer layers of the reaction chamber and the passivation chamber are both provided with a temperature control layer; the drying chamber is provided with an infrared heating device, and the drying is completed in 1-10 seconds; the storage chambers I and II are provided with a temperature control layer; the storage chambers II and III are ... The outer layers of the storage chambers Ⅲ and Ⅳ are all provided with temperature control sleeves; the reaction chamber, passivation chamber and drying chamber are all provided with temperature sensors to meet the temperature monitoring of each chamber; a ventilation gate I and a vent are provided at the left end of the reaction chamber, and a ventilation gate II is provided between the reaction chamber and the passivation chamber. The ventilation gates I and II are opened or closed according to the reaction needs, and the connection or closure between the reaction chamber and the passivation chamber is realized at the same time; a ventilation gate III is provided between the passivation chamber and the drying chamber, and the connection or closure between the passivation chamber and the drying chamber is controlled by opening or closing the ventilation gate III; the outlet of the drying chamber is connected to the collecting chamber; pressure controllers are provided in the collecting chamber, the reaction chamber and the passivation chamber to control the pressure balance in each chamber.

[0007] In the above technical solution, further, a filter I is provided at one end of the passivation chamber opposite to the gate II; and a filter II and a particle screen are provided between the outlet of the drying chamber and the collecting chamber.

[0008] In the above technical solution, further, the pore size of the particle sieve is nanometer-sized, preferably 10-800nm.

[0009] In the above technical solution, further, the filter I and the filter II are filter discs with built-in filtering water or organic reagents.

[0010] In the above technical solution, further, the temperature control layer is provided with a heating element and a cooling element for controlling the temperature increase or decrease in the chamber. Preferably, the temperature range of the temperature control layer is 0 to 25°C; the temperature sensor is respectively connected to the heating element and the cooling element; the temperature control sleeve is provided with a heating element for controlling the temperature increase in the storage chamber.

[0011] In the above technical solution, further, the probe of the temperature sensor is placed in the reaction chamber, the passivation chamber, and the drying chamber.

[0012] In the above technical solution, further, the pressure controller includes a pressure sensor, a controller, and a regulating valve; the probe of the pressure sensor is placed in the reaction chamber, the passivation chamber, and the collection chamber.

[0013] The present invention also provides a method for preparing quantum dots, the method using the device according to any one of claims 1 to 7, comprising the following steps:

[0014] Inject reaction solution I into storage chamber I, and reaction solution II into storage chamber II. The temperature of storage chamber I and storage chamber II is adjusted by the temperature control sleeve to raise the temperature of reaction solution I and reaction solution II to the required temperature. The temperature in the reaction chamber is adjusted to the required temperature by the temperature control layer, and the temperature is maintained constant. Close the ventilation gate I and ventilation gate II, and spray the reaction solution I and reaction solution II into the reaction chamber through the solution spray chamber I and solution spray gun II respectively to react. After the reaction is completed, the temperature control layer stops heating, lowers the temperature of the reaction chamber, and cools and condenses the reactants. Open the ventilation gate I and ventilation gate II, and close the ventilation gate. Door III, inert gas is introduced through the vent, and the cooled reactants are blown into the passivation chamber through ventilation gate II; ventilation gate II is closed, and the passivation modification solution is injected into the storage chamber IV, and sprayed out in a mist state through solution spray gun IV to modify and coat the reactants. After passivation and coating, ventilation gates II and ventilation gates III are opened, and inert gas is introduced into the vent. The inert gas is blown into the passivation chamber to blow the reactants after passivation and coating into the drying chamber through the filter. Drying is completed in 1-10 seconds. After drying, the reactants are blown into the collection chamber through the filter and the particle screen to collect the quantum dots; during the preparation process, the pressure controller of each chamber maintains the pressure balance in each chamber.

[0015] In the above technical solution, further, when doping is required during preparation, the dopant is injected into the storage chamber III and sprayed into the reaction chamber in a mist state through a solution spray gun.

[0016] In the above technical solution, further, when the reaction in the reaction chamber is completed and needs to be cooled extremely quickly, the anti-solvent can be injected into the storage chamber III and cooled to a low temperature, and then sprayed into the reaction chamber in a mist state through a solution spray gun to promote crystallization of the product.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention provides a new device for preparing photosensitizers, which avoids the defects of traditional methods that require special laboratories, combined with multiple equipment assistance, and complex operations to prepare photosensitizers, and cannot timely obtain photosensitizers with adjusted components according to treatment needs. It also avoids the defects that the traditional photosensitizer solution will inevitably change in performance and reduce the treatment effect during the transfer process from the laboratory to the hospital. The device of the present invention integrates preparation, passivation modification, drying, and collection, has no site restrictions, and can be prepared by non-chemical professionals. Solid nanoparticle photosensitizers are directly prepared, which are easy to store and easy to use, and can be directly used to prepare spray preparations for respiratory contact administration, avoiding delays in diagnosis and treatment due to transportation turnover. The device of the present invention is suitable for various indoor environments, has a compact structure, is easy to operate, and can be operated and controlled by non-professionals. When the molecular composition and function of the photosensitizer need to be adjusted, the device of the present invention can be used to complete the synthesis and modification in time according to the adjusted scheme to obtain solid photosensitizers, thereby improving treatment efficiency. In addition, the infrared rapid heating mode is used in the photosensitizer collection process, and the drying step can be completed within a few seconds, which maximizes the maintenance of the photosensitizer characteristics and avoids the possible attenuation caused by traditional thermal resistance heating. This device can realize the design and preparation of photosensitizers with all non-toxic components. The synthesis can be achieved by setting the solution in storage chambers I, II, III, and IV in the device and adjusting the reaction temperature, so that the photosensitizer can achieve therapeutic effects under the premise of easy metabolism, safety and non-toxicity. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Structural diagram of the device of the present invention.

[0020] Figure 2 Spectrum of quantum dots prepared in Example 2.

[0021] Figure 3 Scanning electron microscope image of the quantum dots prepared in Example 2.

[0022] Figure 4 Scanning electron microscope image of the quantum dots prepared in Example 3.

[0023] Figure 5 Schematic diagram of the use scenario of the photosensitizer prepared by the device of the present invention.

[0024] Figure 6 Schematic diagram of photodynamic therapy using photosensitizer prepared by the device of the present invention.

[0025] In the figure, 1. temperature control sleeve, 2. storage chamber I, 3. reaction solution A spray, 4. storage chamber II, 5. reaction solution B spray, 6. storage chamber IV, 71. solution spray gun I, 72. solution spray gun II, 73. solution spray gun IV, 74. solution spray gun III, 8. temperature sensor, 9. vent, 10. storage chamber III, 11. reaction chamber, 12. modification chamber, 13. temperature control layer, 141. ventilation gate I, 142. ventilation gate II, 143. ventilation gate III, 15 . Photosensitizer aerosol after passivation coating, 16. Filter I, 17. Drying chamber, 171. Infrared heating device, 18. Photosensitizer particles after drying, 19. Filter II, 20. Particle sieve, 21. Quantum dot collector, 22. Pressure controller, 23. Filter booster, 24. Atomizing nozzle, 25. Aerosol of quantum dot photosensitizer, 26. Schematic diagram of human respiratory system, 27. Excitation light source, 28. Photosensitizer attached to tumor cells, 29. Photosensitizer solution storage tank. DETAILED DESCRIPTION

[0026] The present invention is further described below in conjunction with specific embodiments, but the present invention is not limited in any way. In the present disclosure, unless otherwise stated, the directional words used, such as "upper", "lower", "left", and "right", are generally defined based on the drawings of the corresponding drawings, and "inside" and "outside" refer to the inside and outside of the corresponding component outline. The terms "first", "second", etc. are used to distinguish one element from another and do not have order and importance. In addition, when the following description refers to the drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements.

[0027] Example 1

[0028] A photosensitizer preparation device comprises a reaction chamber 11, a passivation chamber 12, and a drying chamber 17 connected in sequence; a storage chamber Ⅰ2 and a storage chamber Ⅱ4 are arranged above the reaction chamber, a storage chamber Ⅲ10 is arranged below the reaction chamber, and a storage chamber Ⅳ6 is arranged above the passivation chamber 12; a solution spray gun Ⅰ71, a solution spray gun Ⅱ72, and a solution spray gun Ⅳ73 are arranged below the storage chamber Ⅰ2, the storage chamber Ⅱ4, and the storage chamber Ⅳ6, respectively, and a solution spray gun Ⅲ74 is arranged above the storage chamber Ⅲ; the nozzles of the solution spray gun Ⅰ71, the solution spray gun Ⅱ72, and the solution spray gun Ⅲ74 The solution spray gun IV73 is passed into the reaction chamber, and the nozzle of the solution spray gun IV73 is passed into the passivation chamber 12; the outer layers of the reaction chamber 11 and the passivation chamber 12 are provided with a temperature control layer 13; the outer side of the drying chamber 17 is provided with an infrared heating device 171; the outer layers of the storage chambers I2, II4, III10 and IV6 are provided with a temperature control sleeve 1; the reaction chamber 11, the passivation chamber 12 and the drying chamber 17 are provided with a temperature sensor 8 to meet the temperature monitoring of each chamber; the left end of the reaction chamber 11 is provided with a ventilation gate I141 and a vent 9, and a temperature control device 171 is provided between the reaction chamber and the passivation chamber. Ventilation gate II 142, ventilation gate I 141 and ventilation gate II 142 are opened or closed according to the reaction needs, and the reaction chamber 11 and the passivation chamber 12 are connected or closed at the same time; a gate III 143 is set between the passivation chamber 12 and the drying chamber 17, and the connection or closure between the passivation chamber 12 and the drying chamber 17 is controlled by opening or closing the gate III 143. For example, a slideway can be set on the inner wall of the reaction chamber, the passivation chamber 12 and the drying chamber to match the ventilation gate. The ventilation gate slides on the slideway to achieve the closure and connection of the chamber. The ventilation gate I is opened After that, inert gas can be introduced into the vent; the outlet of the drying chamber 17 is connected to the collecting chamber 21; pressure controllers 22 are arranged in the collecting chamber 21, the reaction chamber 11 and the passivation chamber 12 to control the pressure balance in each chamber; ventilation pipes are arranged between the reaction chamber and the passivation chamber, between the passivation chamber and the drying chamber, and between the drying chamber and the collecting chamber. After each ventilation gate is opened, the reaction chamber, the passivation chamber, the drying chamber and the collecting chamber are connected, and inert gas is introduced through the ventilation pipe; ventilation gate II can be arranged at the left end of the passivation chamber, and ventilation gate III can be arranged at the left end of the drying chamber.

[0029] In order to improve the purity of quantum dots, a filter I16 is optionally provided at the end of the passivation chamber 12 opposite to the gate II142 to filter out unreacted reactants, solvents, etc.; a filter II19 and a particle screen 20 are provided between the outlet of the drying chamber 17 and the collection chamber 21 to remove residual reagents and impurities from the reaction again. The pore size of the particle screen is nanometer-scale, which meets the requirement that the photosensitizer is directly prepared into an aerosol later.

[0030] Optionally, filter I and filter II are filter discs with built-in filtering water or organic reagents to filter residual reagents or impurities.

[0031] Optionally, the temperature control layer is provided with a heating element and a cooling element for controlling the temperature in the chamber to rise or fall, and the temperature range of the temperature control layer is 0 to 25°C; the temperature sensors are respectively connected to the heating element and the cooling element, and the probes of the temperature sensors are respectively placed in the reaction chamber, the passivation chamber, and the drying chamber; after the value is set, the temperature in the chamber is sensed by the temperature sensor, and when the temperature does not meet the requirement, the temperature sensor feeds back the instruction to the heating element or the cooling element, so that they work together to make the temperature in the corresponding chamber reach the required value. The temperature control sleeve is provided with a heating element for heating the storage chamber.

[0032] Optionally, the pressure controller includes a pressure sensor, a controller, and a regulating valve; the probe of the pressure sensor is placed in the reaction chamber 11, the passivation chamber 12, and the collection chamber 21, and the pressure in the chamber is transmitted to the controller through the pressure sensor, and then the pressure in the chamber is balanced through the regulating valve.

[0033] Optionally, the drying chamber is provided with an infrared heating device 171, and the drying is completed in 1-10 seconds, which effectively reduces the damage to the properties of the photosensitizer caused by long-term heating and drying, and ensures the performance of the photosensitizer to the greatest extent.

[0034] The method of preparing quantum dots using the above device includes the following steps:

[0035] The reaction solution I is injected into the storage chamber I, and the reaction solution II is injected into the storage chamber II. The temperature of the storage chamber I and the storage chamber II is adjusted by the temperature control sleeve to raise the reaction solution I and the reaction solution II to the desired temperature. The temperature in the reaction chamber is raised to the desired temperature by the temperature control layer and the temperature is maintained constant. The ventilation gate I and the ventilation gate II are closed, and the reaction solution I and the reaction solution II are sprayed into the reaction chamber through the solution spray chamber I and the solution spray gun II respectively to react. After the reaction is completed, the temperature control layer stops heating, lowers the temperature of the reaction chamber, and cools and condenses the reactants. The ventilation gates I and II are opened. Ventilation gate II, close vent gate III, pass inert gas through the vent, blow the cooled reactant to the passivation chamber through vent gate II; close vent gate II, inject the passivation modification solution into storage chamber IV, spray it out in a mist state through solution spray gun IV, modify and coat the reactant, after passivation coating, open vent gate II and vent gate III, pass inert gas through the vent, blow inert gas into the passivation chamber, passivation coated reactant into the drying chamber through the filter, infrared heating device is set to complete drying for 7s, after drying, blow into the collection chamber through the filter and particle screen to collect photosensitizer. When doping is required during preparation, inject the dopant into storage chamber III, spray it into the reaction chamber in a mist state through the solution spray gun, and exchange the anions and cations in the molecule by ion exchange (for example, replace I ions with Br ions, replace Pb ions with Mn ions, etc.) to prepare the required perovskite quantum dots. During the preparation process, the pressure controller of each chamber maintains the pressure balance in each chamber.

[0036] The solid photosensitizer prepared by the present invention is dispersed in a solvent again when it is needed, and is loaded into a photosensitizer solution storage tank 29 of a spray device, and connected to a stainless steel spray nozzle 24 through a filter booster 23, such as Figure 5 The spray device includes a storage tank 29, a filter booster 23, and a nozzle 24. The storage tank 29 is connected to the filter booster 23, and the filter booster 23 is connected to the nozzle 24. The atomization pressure and the injection pressure are usually 0.01-3MPa, and the distance between the nozzle and the human mouth and nose is about 5-25cm. The sprayed aerosol is an aerosol 25 containing a quantum dot photosensitizer, wherein the scale of the photosensitizer is below the micron level, the typical size is 10-800nm, and the nozzle speed is about 1-20mm / s. The photosensitizer 28 modified with the targeting molecule reaches the human respiratory tract through the breathing process and combines with the tumor cells. Subsequently, the light source 27 is introduced to irradiate the tumor affected area for photodynamic therapy, such as Figure 6 According to the patient's specific condition, the amount of photosensitizer solution inhaled can be adjusted.

[0037] Example 2

[0038] The device of the present invention is used to prepare a completely non-toxic element photosensitizer:

[0039] 0.4mmol of tin bromide was dissolved in 10ml of N,N-dimethylformamide (DMF, 99.8%), and 1.6mmol of N,N′-dimethylethylene-1,2-dibromide was dissolved in 20ml of DMF. After forming clear precursor solutions, they were respectively injected into storage chamber Ⅰ2 and storage chamber Ⅱ4. 600ml of dichloromethane (DCM, 99.9%) was placed in solution storage chamber Ⅲ10. The temperature control jacket 1 heated the temperature to 45°C, and the temperature of the reaction chamber 11 was controlled at 45°C, and the temperature was controlled constant by the temperature sensor 8. The ventilation gate Ⅰ141 and the ventilation gate Ⅱ142 were closed, and the solutions in the storage chamber Ⅰ2 and the storage chamber Ⅱ4 were sprayed through the solution spray gun Ⅰ71 and the solution spray gun Ⅱ72 to form spray 3 and spray 5, and reacted in the reaction chamber 11. After the reaction, the temperature in the reaction chamber 11 is adjusted to 0°C, and the DCM solution in the storage chamber III10 is cooled to 0°C. After being quickly sprayed out by the solution spray gun III74, the reaction product is cooled and condensed to form C 16 H 56 N8Nb 10Crystals. Open the ventilation gates Ⅰ141 and Ⅱ142, close the ventilation gate Ⅲ, introduce inert gas N2 into the reaction chamber 11 through the vent 9, use the N2 gas flow to purge the generated quantum dots into the passivation modification chamber 12, close the ventilation gate Ⅱ142, spray the solution in the passivation modification solution storage chamber Ⅳ6 in a mist state through the solution spray gun Ⅳ73, further modify and coat the quantum dots, and form the passivation coated photosensitizer mist 15. Open the ventilation gates Ⅰ, Ⅱ, and Ⅲ, and as N2 is purged through the reactant filter Ⅰ16 to filter out the reactants and solvents, enter the drying chamber 17, and the infrared heating device completes the drying in 10s to obtain the dried photosensitizer particles 18. Then pass through the filter Ⅱ19 and the particle screen 20 to remove the residual reagents and impurities of the reaction again, set a 150nm aperture particle screen for screening, so that the size of the photosensitizer is controlled below 150nm, and finally reach the quantum dot collector 21. Filter I and filter II are used to remove residual reagents or impurities in the reaction process to improve the purity of the photosensitizer. The filter can be built with an activated carbon film or a dry film or a combination of the two films, or different films that can remove these substances can be selected according to the different residual reagents and impurities produced in different reaction processes; during the entire reaction process, the pressure balance in each chamber is controlled by a pressure controller. The yield of the reaction is about ~72%. The quantum dots synthesized by the above method have an emission peak centered at about 570nm, a half-peak width of about 105nm, and a fluorescence quantum yield of about 90% under 350nm laser irradiation. Figure 2 As shown. The scale is 25-300nm, such as Figure 3 Scanning electron microscope photos shown.

[0040] The collected solid C 16 H 56 N8Nb 10 The quantum dot photosensitizer is dispersed into the solvent again, loaded into the photosensitizer solution storage tank 29 of the spray device, and connected to the stainless steel spray nozzle 24 through the filter booster 23. The atomization pressure and the spray pressure are usually 0.01-3MPa, and the distance between the nozzle and the human mouth and nose is about 5-25cm. The sprayed aerosol is an aerosol 25 containing quantum dot photosensitizer, the size of the photosensitizer is below 150nm, and the speed of the nozzle is about 1-10mm / s. The photosensitizer 28 modified with the targeting molecule reaches the human respiratory tract through the breathing process and combines with nasopharyngeal carcinoma tumor cells. Subsequently, the light source 27 is introduced to irradiate the tumor affected area for photodynamic therapy, such as Figure 6 According to the patient's specific condition, the course of treatment and the amount of photosensitizer solution inhaled can be adjusted.

[0041] Example 3

[0042] The device of the present invention is used to prepare a completely non-toxic element photosensitizer:

[0043] 0.1mmol Ag(ac), Na(ac) (200uL sodium oleate stock solution), 0.2mmol In(ac)3, 40uL Bi(ac)3, 100μL HCl, 2.0mL degassed oleylamine (OLAM); 1.76mL degassed oleic acid (OA) and 8ml ODE were mixed and dissolved, heated to 110℃ under vacuum to remove residual air and water, and then injected into storage chamber Ⅰ2, and the temperature was controlled to room temperature. 1mL cesium oleate solution was injected into storage chamber Ⅱ4, and the temperature of reaction chamber 11 was controlled at room temperature. Ventilation gate Ⅰ141 and venting gate Ⅱ142 were closed, and according to the chemical formula ratio, the solution in storage chamber Ⅰ2 and storage chamber Ⅱ4 was sprayed through solution spray gun Ⅰ71 and solution spray gun Ⅱ72 to form spray 3 and 5, and reacted in reaction chamber 11. After 10 minutes at room temperature, the system was heated to 210℃ at a rate of 0.5℃ / s by the temperature controller. After the reaction is fully completed for 15-45 minutes, the temperature control layer 13 is lowered to room temperature to cool and condense the reactants to form Cs2Ag 0.5 Na 0.5 InCl6 crystals. Open the ventilation gate Ⅰ141 and the ventilation gate Ⅱ142, and introduce inert gas N2 into the vent 9. Use the N2 gas flow to blow the generated quantum dots into the passivation modification chamber 12. Close the ventilation gate Ⅰ141 and the ventilation gate Ⅱ142, and spray the solution in the passivation modification solution storage chamber 6 in a mist state through the solution spray gun Ⅳ73 to further modify and coat the quantum dots to form the passivation coated photosensitizer mist 15. Subsequently, open the ventilation gate Ⅰ141, the ventilation gate Ⅱ142, and the ventilation gate Ⅲ143, introduce N2, filter out the reactants and solvents through the reactant filter Ⅰ16, enter the drying chamber 17, and complete the drying with the infrared heating device 9s to obtain the dried photosensitizer particles 18. The particle size of the photosensitizer is then screened through the filter II 19 and the particle screen 20, and a 300nm aperture particle screen is set for screening to control the size of the photosensitizer below 300nm, and the residual reaction reagents and impurities are removed again before finally reaching the quantum dot collector 21. During the entire reaction process, the pressure balance in each chamber is controlled by a pressure controller.

[0044] Among them, the preparation methods of several solutions involved are as follows:

[0045] Preparation of cesium oleate stock solution:

[0046] 1304 mg of Cs2CO3 and 20 mL of OA were placed in a glass container, heated to 110°C, and the mixture was degassed under vacuum until Cs2CO3 was completely dissolved to form a colorless and transparent reaction solution.

[0047] Preparation of bismuth oleate stock solution:

[0048] 309 mg Bi(ac)3 and 8 ml OA were placed in a glass container, heated to 110°C, and the mixture was degassed under vacuum until it dissolved to form a colorless and transparent reaction solution.

[0049] Preparation of sodium oleate stock solution:

[0050] 164 mg of Na(ac) and 4 ml of OA were placed in a glass container, heated to 110° C., and the mixture was degassed under vacuum until it dissolved to form a colorless and transparent reaction solution.

[0051] Cs2Ag synthesized by the above method 0.5 Na 0.5 InCl6 quantum dots, the size of which is about 150-650nm according to SEM observation, Figure 4 Scanning electron microscope photos show that under 340nm laser irradiation, the center of the emission peak is near 550nm, the half-peak width is about 150nm, and the fluorescence quantum yield is about 95%.

[0052] The collected solid Cs2Ag 0.5 Na 0.5 The InCl6 quantum dot photosensitizer is dispersed into the solvent again, loaded into the photosensitizer solution storage tank 29 of the spray device, and connected to the stainless steel spray nozzle 24 through the filter booster 23, such as Figure 5 The atomization pressure and the spray pressure are usually 0.01-3MPa, and the distance between the nozzle and the human mouth and nose is about 5-25cm. The sprayed aerosol is an aerosol 25 containing quantum dot photosensitizer, wherein the size of the photosensitizer is about 200nm, and the nozzle speed is about 5-20mm / s. The photosensitizer 28 modified with the targeting molecule reaches the lung tumor tissue through the respiratory tract, and then the light source 27 is introduced to irradiate the tumor site for photodynamic therapy of lung squamous cell carcinoma, such as Figure 6 According to the patient's specific condition, the course of treatment and the amount of photosensitizer solution inhaled can be adjusted.

[0053] The device of the present invention can be used to prepare photosensitizers synthesized from different components, is suitable for preparation under various reaction conditions, integrates particle preparation, modification and coating, purification and drying, and can directly prepare photosensitizers that meet treatment needs in terms of components and structure, thereby meeting subsequent treatment needs. The device is simple to operate, does not require professional technicians, can be directly prepared at the treatment site, and meets the need for timely adjustment of photosensitizer components for preparation.

[0054] For any technician familiar with the art, without departing from the scope of the technical solution of the present invention, the technical content disclosed above can be used to make many possible changes and modifications to the technical solution of the present invention, or modified into equivalent embodiments with equivalent changes. Therefore, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention should still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A photosensitizer preparation device, characterized in that: The invention comprises a reaction chamber (11), a passivation chamber (12), and a drying chamber (17) which are connected in sequence; a storage chamber I (2) and a storage chamber II (4) are arranged above the reaction chamber, a storage chamber III (10) is arranged below the reaction chamber, and a storage chamber IV (6) is arranged above the passivation chamber (12); a solution spray gun I (71), a solution spray gun II (72), and a solution spray gun IV (73) are arranged below the storage chamber I (2), the storage chamber II (4), and the storage chamber IV (6), respectively; a storage chamber III (10) is arranged above the storage chamber I (2), the storage chamber II (4), and the storage chamber IV (6). A solution spray gun III (74) is provided on the side; the spray heads of the solution spray guns I (71), II (72) and III (74) are connected to the reaction chamber, and the spray head of the solution spray gun IV (73) is connected to the passivation chamber (12); the outer layers of the reaction chamber (11) and the passivation chamber (12) are provided with a temperature control layer (13); the drying chamber (17) is provided with an infrared heating device (171); the outer layers of the storage chambers I (2), II (4), III (10) and IV (6) are provided with a temperature control layer (13 ... Each of the reaction chamber (11), the passivation chamber (12) and the drying chamber (17) is provided with a temperature sensor (8) to meet the temperature monitoring of each chamber; a ventilation gate I (141) and a vent (9) are provided at the left end of the reaction chamber (11), and a ventilation gate II (142) is provided between the reaction chamber (11) and the passivation chamber (12); the ventilation gate I (141) and the ventilation gate II (142) are opened or closed according to the reaction requirements, and the reaction chamber is simultaneously controlled. The invention relates to a method for controlling the connection or closure between the passivation chamber (11) and the passivation chamber (12); a ventilation gate III (143) is arranged between the passivation chamber (12) and the drying chamber (17); the connection or closure between the passivation chamber (12) and the drying chamber (17) is controlled by opening or closing the ventilation gate III (143); the outlet of the drying chamber (17) is connected to the collection chamber (21); and a pressure controller (22) is arranged in each of the collection chamber (21), the reaction chamber (11) and the passivation chamber (12) to control the pressure balance in each chamber.

2. The device for preparing a photosensitizer according to claim 1, characterized in that: A filter I (16) is provided at the end of the passivation chamber (12) opposite to the gate II (142); a filter II (19) and a particle screen (20) are provided between the outlet of the drying chamber (17) and the collecting chamber (21).

3. The device for preparing a photosensitizer according to claim 2, characterized in that: The pore size of the particle sieve is nanometer size.

4. The device for preparing a photosensitizer according to claim 2, characterized in that: The filter I and filter II are filter discs with built-in filtering water or organic reagents.

5. The device for preparing a photosensitizer according to claim 1, characterized in that: The temperature control layer is provided with a heating element and a cooling element for controlling the temperature in the chamber to rise or fall. Preferably, the temperature range of the temperature control layer is 0 to 25° C.; the temperature sensor (8) is connected to the heating element and the cooling element respectively; the temperature control sleeve is provided with a heating element for controlling the temperature rise in the storage chamber.

6. The device for preparing a photosensitizer according to claim 1, characterized in that: The probe of the temperature sensor (8) is placed in the reaction chamber (11), the passivation chamber (12), and the drying chamber (17).

7. The device for preparing a photosensitizer according to claim 1, characterized in that: The pressure controller comprises a pressure sensor, a controller, and a regulating valve; the probe of the pressure sensor is placed in the reaction chamber (11), the passivation chamber (12), and the collection chamber (21).

8. A method for preparing a photosensitizer, characterized in that: The method uses the device according to any one of claims 1 to 8, comprising the following steps: Inject reaction solution I into storage chamber I, inject reaction solution II into storage chamber II, adjust the temperature of storage chamber I and storage chamber II by temperature control sleeve to raise reaction solution I and reaction solution II to required temperature, raise the temperature in reaction chamber to required temperature by temperature control layer, and maintain constant temperature; close ventilation gate I and ventilation gate II, spray reaction solution I and reaction solution II into reaction chamber through solution spray chamber I and solution spray gun II respectively to react; after reaction, stop heating at temperature control layer, lower temperature in reaction chamber, and cool and condense reactant; open ventilation gate I and ventilation gate II, close ventilation gate Ⅲ, introduce inert gas through the vent, and blow the cooled reactants into the passivation chamber through the vent gate Ⅱ; close the vent gate Ⅱ, inject the passivation modification solution into the storage chamber Ⅳ, and spray it out in a mist state through the solution spray gun Ⅳ to modify and coat the reactants. After passivation and coating, open the vent gates Ⅱ and Ⅲ, introduce inert gas through the vent, blow the inert gas into the passivation chamber, and blow the reactants after passivation and coating into the drying chamber through the filter. The drying is completed in 1-10 seconds. After drying, the reactants are blown into the collection chamber through the filter and the particle screen to collect the quantum dots; during the preparation process, the pressure controller of each chamber maintains the pressure balance in each chamber.

9. The method for preparing a photosensitizer according to claim 8, characterized in that: When doping is required during preparation, the dopant is injected into the storage chamber III and sprayed into the reaction chamber in a mist state through a solution spray gun.

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