Preparation process for supramolecular carrier photosensitizer for photodynamic therapy, and formulation thereof

Abstract

The present invention relates to the field of anti-inflammatory and antiseptic formulations for prevention and treatment of dental diseases in the department of stomatology, and specifically to a preparation process for a supramolecular carrier photosensitizer for photodynamic therapy, and a formulation thereof. A supramolecular carrier is composed of refined lignin, glucomannan, cysteine, and sodium benzoate at the mass ratio of 0.1-1.0%:0.5-3%:0.1-0.5%:0.05%, with the balance of water. The preparation process comprises: first respectively preparing aqueous solutions of refined lignin, glucomannan, cysteine, and sodium benzoate; then adjusting the pH value of a mixed solution to 6.5, so that dissolved alkali lignin is separated out, so as to form an efficient and stable three-dimensional polymer network framework; and promoting formation of abundant hydrogen bonds between identical molecules and different molecules of lignin and glucomannan, so as to prepare a photosensitizer-loaded supramolecular carrier formulation. The present invention can ensure the long-term storage stability of the physical and chemical properties of the formulation, and is conducive to quickly promoting the application of PDT in the anti-inflammatory and sterilization treatment of dental diseases in the department of stomatology.

Description

Preparation process of supramolecular carrier photosensitizer for photodynamic therapy and preparation thereof TECHNICAL FIELD

[0001] The present application relates to a preparation process of supramolecular carrier photosensitizer for photodynamic therapy and preparation thereof, and belongs to the field of anti-inflammatory and sterilization preparations for dental disease prevention and treatment. BACKGROUND

[0002] Bacterial infection is an important factor leading to the development of inflammation in gingival, periodontal, dental pulp and periapical tissue. Due to the particularity of the oral environment, the composition of pathogenic bacteria in oral lesions is complex, and these bacteria exist in the form of biofilm at the lesion site, making it very difficult to eradicate. Therefore, removing or killing pathogenic bacteria is an inevitable way to prevent and treat dental diseases. Currently, the conventional treatment methods for dental anti-inflammatory and sterilization mainly include antibiotic therapy, surgical treatment and preoperative sterilization solution irrigation. Local application or oral administration and injection of antibiotics have serious drug resistance, thus affecting the curative effect of multiple treatments. Basic treatment and surgical treatment can cause gum damage and root surface sensitivity. The commonly used preoperative sodium hypochlorite solution has good sterilization effect, but its diffusion depth is limited in narrow root canal, and the cleaning and sterilization effect is restricted. Moreover, sodium hypochlorite has corrosive and cytotoxic properties, which can easily damage the soft tissue in contact with it, and even the airway.

[0003] The conventional treatment methods for dental inflammation and sterilization mainly include preoperative disinfectant irrigation, scaling surgery and antibiotic therapy. Unlike conventional treatment methods, the sterilization principle of photodynamic therapy (PDT) is based on the energy absorption of photosensitizer at a specific wavelength of light to become an excited state, and then release energy during the transition back to the ground state to activate tissue oxygen, and use the cytotoxicity of active oxygen to achieve the effect of inflammation and sterilization. Based on a large number of in vitro and in vivo evaluations, the effect of PDT in treating gingival porphyromonas gingivalis is more accurate, and compared with the current conventional treatment methods, PDT has outstanding advantages in reducing treatment damage, reducing side effects, overcoming drug resistance, etc. In recent years, the application of PDT in the treatment of dental diseases has attracted great attention in the industry, and important progress has been made in its clinical application. As one of the key applications of PDT, the photosensitizer preparation, toluidine blue and its gel combination dosage form has developed the fastest. First, the photosensitizer toluidine blue has no obvious toxic side effects. Second, toluidine blue is a nucleic acid-preferring acidophilic dye with good selective adsorption in diseased areas and pathogenic bacteria, which can avoid normal tissue damage by photodynamic killing. Third, the gel preparation has certain viscosity and adhesion, which can constrain the photosensitizer to stay in the diseased area to improve the treatment effect, and can further ensure that the normal tissue is not damaged during the treatment process from the dosage form. Patent CN106822894A discloses a photosensitizer preparation formula and application for photodynamic treatment of periodontitis, and the photosensitizer preparation mainly consists of toluidine blue, carbomer, sodium hydroxide or triethanolamine, wherein carbomer is the gel component in the preparation. Patent CN108042544B discloses a toluidine blue photodynamic sterilization and healing promoting composition and its application. The composition consists of toluidine blue, sodium hyaluronate and chitosan in a mass ratio of 1:(0.1-2):(0.5-10), wherein sodium hyaluronate and chitosan are the gel components in the preparation. The research results show that these combination dosage forms for periodontal, gingival disease prevention and treatment and oral postoperative wound sterilization show excellent treatment effect. However, low content, low viscosity gel, especially physical gel, has the trend of becoming unstable due to phase separation during long-term storage, which is a common adverse factor affecting the qualified rate of gel photosensitizer dosage form products.

[0004] In view of the above possible problems, the present application introduces biomass lignin containing rich oxygen-containing active groups to construct an efficient and stable supramolecular network in the photosensitizer preparation, aiming to develop a long-term stable photosensitizer preparation for gingival and periodontal positioning anti-inflammatory and sterilization and its production process. To ensure that the preparation does not have problems such as surface skinning, flocculation precipitation, viscosity reduction and other quality index unqualified problems during long-term storage.

[0005] SUMMARY

[0006] The present application aims to provide a preparation process of a supramolecular carrier photosensitizer for photodynamic therapy of inflammation and sterilization of oral gingival, periodontitis, peri-implantitis and pulpitis, and a preparation thereof, so as to overcome the deficiencies in the prior art.

[0007] The technical principle of the present application is that lignin is one of the components constituting the plant cell wall and has the function of connecting cells. Lignin is a biological macromolecule with a three-dimensional network structure formed by the mutual connection of three phenylpropane units through ether bonds and carbon-carbon bonds, and contains a large number of active groups such as aromatic groups, phenolic hydroxyl groups, alcoholic hydroxyl groups, and carbon-carbon double bonds in the molecule. It is easily soluble in water in the form of sodium or potassium salt under strong alkaline conditions, and under acidic conditions, H + The substituted metal ions form a large number of hydrogen bonds between molecules and then precipitate. The present application utilizes the characteristics of the alkali dissolution and acid precipitation method of lignin, and the refined lignin precipitated at a pH of 7.5 to 6.5 has a more uniform molecular weight distribution. The addition of refined lignin to the preparation system forms a stable three-dimensional network structure under the condition of pH 6.5. The stability of this three-dimensional network structure may be partially destroyed only under the condition of increased pH, and its stability is irreversible and is not affected by temperature, temperature, storage time, etc. Moreover, a large number of oxygen-containing groups on the lignin form intermolecular hydrogen bonds with the abundant hydroxyl groups of glucomannan. Thus, the long-term stability of the preparation is ensured.

[0008] The technical solution adopted by the present application is as follows: a preparation process of a supramolecular carrier photosensitizer, comprising the following steps:

[0009] Step 1: Take a specified amount of distilled water and add a certain amount of glucomannan, stir at room temperature until the glucomannan is completely swollen and dispersed, and reserve;

[0010] Step 2: Take a specified amount of distilled water and add a certain amount of biomass refined lignin, stir at room temperature while adjusting the pH value to the range of 7.5-9.0 with baking soda until complete dissolution to obtain a refined lignin solution, and reserve;

[0011] Step 3: Take a specified amount of distilled water, dissolve the photosensitizer in the distilled water to prepare a photosensitizer aqueous solution with a concentration of 200-1000 mg / L, then add a certain amount of cysteine, and stir at room temperature until complete dissolution, and reserve;

[0012] Step 4: Weigh a certain amount of sodium benzoate and add it to a specified amount of distilled water, stir until the sodium benzoate is completely dissolved, and reserve;

[0013] Step 5: Mix the four solutions prepared in the preceding steps uniformly, and add acetic acid to adjust the pH value to 6.0-6.5;

[0014] Step 6, place in a water bath, heat to 45-65℃ and keep constant temperature for 5-48 hours, and naturally cool to obtain the supramolecular carrier loaded photosensitizer preparation.

[0015] The refined lignin is prepared by an alkali dissolution and acid precipitation method, and the lignin is separated and purified at a pH value in the range from 7.5 to 6.5 in the acid precipitation process.

[0016] Step 1, disperse the raw lignin in water, add sodium hydroxide solution while stirring to adjust the pH value to ≥ 11.0, and continue to stir until completely dissolved;

[0017] Step 2, filter to remove insoluble impurities;

[0018] Step 3, add sulfuric acid solution while stirring in the filtrate to adjust the pH value to 7.5, continue to stir for a period of time, then filter out the precipitated lignin, and reserve the filtrate;

[0019] Step 4, slowly add dilute sulfuric acid solution while stirring in the collected filtrate to adjust the pH value to 6.5, filter, and the filtrate is washed repeatedly with distilled water, dried to obtain the refined lignin.

[0020] The raw lignin of the refined lignin includes any one of enzymatic lignin, organic solvent lignin, ground wood lignin, alkali lignin and kraft lignin.

[0021] The photosensitizer is at least one of silica sol gel-based toluidine blue O, toluidine blue and methylene blue, which is prepared from the following components in mass percentage: 0.001-0.1% of toluidine blue O, 2-15% of nano-silicon dioxide, and the balance of physiological saline;

[0022] The nano-silicon dioxide includes hydrophilic silicon dioxide and hydrophobic silicon dioxide, and the hydrophilic and hydrophobic silicon dioxide is adjusted to control the hydrophilicity and lipophilicity of the photosensitive combination agent.

[0023] The nano-silicon dioxide includes fumed silicon dioxide and liquid-phase silicon dioxide.

[0024] The fumed silicon dioxide is amorphous, and the initial particle size is 7-40 nanometers.

[0025] The porosity of the liquid-phase silicon dioxide is 95%-99.8%, and the specific surface area is >1000 m 2 / g.

[0026] The liquid-phase silicon dioxide is produced by a sol-gel method, and the supporting drying process adopts freeze drying or supercritical drying.

[0027] The preparation method of the photosensitizer comprises the following steps:

[0028] Step 1, dissolve at least one of the silicon sol gel-based toluidine blue O, toluidine blue and methylene blue in a specified amount of 85% sodium chloride physiological saline;

[0029] Step 2, using a high-speed disperser, slowly add a specified amount of nano-silicon dioxide under stirring at a stirring speed of 50-100 rpm, and continue stirring for 5 minutes after the addition is completed;

[0030] Step 3, gradually adjust the speed to 3000-5000 rpm, and continue stirring in the high-speed disperser for 10 minutes to ensure uniform dispersion;

[0031] Step 4, stop stirring, add the remaining 15% physiological saline, rinse the inner wall of the container while adding, and then stir at a low speed of 100 rpm for 10 minutes to obtain the photosensitizer.

[0032] It also includes a photosensitizer combination agent, and the effective components include photosensitizer, saccharide component, and penetrant, with a mass percentage of 1:(10-200):(0-5);

[0033] The photosensitizer combination agent uses physiological saline as a solvent, and the mass percentage of the effective components is 0.5% to 5%; the viscosity of the photosensitizer combination agent is 5 to 5000 mPa·s.

[0034] The preparation method of the photosensitizer combination agent comprises the following steps:

[0035] Step 1, dissolve the photosensitizer in sodium chloride physiological saline;

[0036] Step 2, add the saccharide component; dissolve or swell, and stir to mix evenly;

[0037] Step 3, add the penetrant; mix evenly under stirring;

[0038] Step 4, make up the physiological saline to 100% of the total mass percentage, and obtain the final combination agent after sufficient stirring.

[0039] When the combination agent is applied to photodynamic inflammation and sterilization treatment of root canals, it is a low-viscosity preparation; the viscosity is 3 to 100 mPa·s, including 3 mPa·s and 100 mPa·s; and more preferably, the viscosity is 5 to 10 mPa·s;

[0040] When the combination agent is applied to photodynamic inflammation and sterilization treatment of periodontal pockets, it is a medium-viscosity preparation; the viscosity is 100 to 1800 mPa·s, including 1800 mPa·s; and more preferably, the viscosity is 500 to 1000 mPa·s;

[0041] The combination agent applied to the photodynamic inflammation and sterilization treatment of the gingival surface is a high viscosity preparation; the viscosity is located at 1800 to 5000 mPa·s, including 5000 mPa·s; and the viscosity is preferably 2500 to 3000 mPa·s.

[0042] The preparation is composed of refined lignin, glucomannan, cysteine and sodium benzoate in a mass ratio of 0.1-1.0%:0.5-3%:0.1-0.5%:0.05-0.2%, and the rest is water.

[0043] The supermolecular structure carrier of the preparation is composed of lignin and glucomannan in a complex manner, the efficient three-dimensional supermolecular network structure constructed by refined lignin is not easily affected by storage conditions and environmental changes such as temperature, humidity, time and light, which ensures the long-term stability of the physical and chemical properties of the photosensitizer carrier. The long-term storage stability of ordinary gel preparations, especially low-content and low-viscosity physical gel preparations, is easily affected by environmental temperature, time and other factors. Compared with ordinary gel-loaded photosensitizer preparations, the preparation of the present application has the advantages of ordinary gel preparations and ensures the long-term storage stability of the physical and chemical properties of the preparation. The product qualification rate is a key factor for the application of the preparation, so the present application is beneficial to the rapid application of PDT in oral inflammation and sterilization treatment. DETAILED DESCRIPTION

[0044] To make the purpose, technical scheme and advantages of the present application more clear and obvious, the present application is further described in detail below in combination with specific embodiments and with reference to the drawings. It should be understood that these descriptions are only exemplary and do not limit the scope of the present application. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present application.

[0045] The technical scheme adopted by the present application is as follows: a supermolecular carrier photosensitizer preparation process, comprising the following steps:

[0046] Step 1: Take a specified amount of distilled water and add a certain amount of glucomannan, stir at room temperature until the glucomannan is completely swollen and dispersed, and prepare for use;

[0047] Step 2: Take a specified amount of distilled water and add a certain amount of biomass refined lignin, stir and adjust the pH value to 7.5-9.0 with baking soda at room temperature until the refined lignin is completely dissolved to obtain a refined lignin solution, and prepare for use;

[0048] Step 3, take a specified amount of distilled water, dissolve the photosensitizer in the distilled water to prepare a photosensitizer aqueous solution of 200 mg / L to 1000 mg / L, then add a certain amount of cysteine, stir at room temperature until completely dissolved, and reserve;

[0049] Step 4, weigh a certain amount of sodium benzoate into a specified amount of distilled water, stir until the sodium benzoate is completely dissolved, and reserve;

[0050] Step 5, mix the four solutions prepared in the preceding steps uniformly, add acetic acid to adjust the pH value to 6.0-6.5;

[0051] Step 6, place in a water bath, heat to 45-65℃ and keep constant temperature for 5-48 hours, and naturally cool to obtain the supermolecular carrier loaded photosensitizer preparation.

[0052] The refined lignin is prepared by an alkali dissolution and acid precipitation method, and the lignin is separated and purified at a pH value in the range from 7.5 to 6.5 during the acid precipitation process.

[0053] Step 1, disperse the raw lignin in water, add sodium hydroxide solution to adjust the pH value to ≥11.0 while stirring, and continue to stir until completely dissolved;

[0054] Step 2, filter to remove insoluble impurities;

[0055] Step 3, add sulfuric acid solution to the filtrate while stirring, adjust the pH value to 7.5, continue to stir for a period of time, then filter out the precipitated lignin, and reserve the filtrate;

[0056] Step 4, in the collected filtrate, slowly add dilute sulfuric acid solution while stirring, adjust the pH value to 6.5, filter, and wash the filtrate repeatedly with distilled water, dry to obtain the refined lignin.

[0057] The raw lignin of the refined lignin includes any one of enzymatic lignin, organic solvent lignin, ground wood lignin, alkali lignin and kraft lignin.

[0058] The photosensitizer is at least one of silica sol gel-based toluidine blue O, toluidine blue and methylene blue, which is prepared from the following components in mass percentage: 0.001-0.1% of toluidine blue O, 2-15% of nano-silicon dioxide, and the balance of physiological saline;

[0059] The nano-silicon dioxide includes hydrophilic silicon dioxide and hydrophobic silicon dioxide, and the hydrophilic and hydrophobic silicon dioxide is adjusted to control the hydrophilicity and lipophilicity of the photosensitive combination agent.

[0060] The nano-silicon dioxide includes fumed silicon dioxide and liquid-phase silicon dioxide.

[0061] The fumed silica is amorphous, with an initial particle size of 7-40 nm;

[0062] The liquid-phase silica has a porosity of 95%-99.8% and a specific surface area of >1000 m 2 / g;

[0063] The liquid-phase silica is produced by a sol-gel method, and the matching drying process uses freeze drying or supercritical drying.

[0064] The photosensitizer preparation method comprises the following steps:

[0065] Step 1: Dissolve at least one of toluidine blue O, toluidine blue and methylene blue in a specified amount of 85% sodium chloride physiological saline to form a silicon sol gel;

[0066] Step 2: Slowly add a specified amount of nano-silica to the silicon sol gel under stirring at a stirring speed of 50-100 rpm using a high-speed disperser, and continue stirring for 5 minutes after the addition is completed;

[0067] Step 3: Gradually adjust the stirring speed to 3000-5000 rpm, and continue stirring in the high-speed disperser for 10 minutes to ensure uniform dispersion;

[0068] Step 4: Stop stirring, add the remaining 15% of the physiological saline, rinse the inner wall of the container while adding, and then stir at a low speed of 100 rpm for 10 minutes to obtain the photosensitizer.

[0069] The photosensitizer combination agent also comprises a photosensitizer, a saccharide component and a penetrant, and has a mass percentage of 1:(10-200):(0-5).

[0070] The photosensitizer combination agent uses physiological saline as a solvent, and the mass percentage of the effective components is 0.5%-5%; the viscosity of the photosensitizer combination agent is 5-5000 mPa·s.

[0071] The photosensitizer combination agent preparation method comprises the following steps:

[0072] Step 1: Dissolve the photosensitizer in sodium chloride physiological saline;

[0073] Step 2: Add the saccharide component; dissolve or swell, and stir to mix uniformly;

[0074] Step 3: Add the penetrant; mix uniformly under stirring;

[0075] Step 4: Add physiological saline to a total mass percentage of 100%, and obtain the final combination agent after sufficient stirring.

[0076] The combination agent is a low viscosity preparation when applied to photodynamic inflammation and sterilization treatment of root canal; the viscosity is 3-100 mPa·s, including 3 mPa·s and 100 mPa·s; and the more preferred viscosity is 5-10 mPa·s;

[0077] The combination agent is a medium viscosity preparation when applied to photodynamic inflammation and sterilization treatment of periodontal pocket; the viscosity is 100-1800 mPa·s, including 1800 mPa·s; and the more preferred viscosity is 500-1000 mPa·s;

[0078] The combination agent is a high viscosity preparation when applied to photodynamic inflammation and sterilization treatment of gingival surface; the viscosity is 1800-5000 mPa·s, including 5000 mPa·s; and the more preferred viscosity is 2500-3000 mPa·s.

[0079] The combination agent is composed of refined lignin, glucomannan, cysteine, sodium benzoate, and water, with a mass ratio of 0.1-1.0%:0.5-3%:0.1-0.5%:0.05-0.2%.

[0080] Example 1:

[0081] Step 1: Measure 100 mL of distilled water, then add 2.0 grams of glucomannan, stir at room temperature for 24 hours until the glucomannan is completely swollen and dispersed, and the resulting solution is named 1-A;

[0082] Step 2: Take 90 mL of distilled water, add 1.2 grams of refined lignin, and adjust the pH value to 7.5-8.0 with baking soda solution while stirring at room temperature, continue stirring until the lignin is completely dispersed and dissolved, then add distilled water to 100 mL, and the resulting solution is named 1-B;

[0083] Step 3: Take 100 mL of distilled water, weigh 20 mg of toluidine blue O and dissolve it in distilled water, then add 0.4 grams of cysteine and stir at room temperature until it is completely dissolved, and the resulting solution is named 1-C;

[0084] Step 4: Weigh 0.2g of sodium benzoate and add it to 100 mL of distilled water to prepare a solution, and stir magnetically until the sodium benzoate is completely dissolved, and the resulting solution is named 1-D;

[0085] Step 5: Add solution 1-B to solution 1-A while stirring, then add solutions 1-C and 1-D, stir until uniform, add acetic acid to adjust the pH value to 6.5, and the resulting intermediate sample is named 1-E;

[0086] Step 6, in a water bath, the intermediate sample 1-E was heated to 45℃ and kept for 20 hours, then naturally cooled to obtain the supramolecular carrier photosensitizer preparation.

[0087] The composition ratio of each component in the preparation is toluene blue O, refined lignin, glucomannan, cysteine, sodium benzoate, with a mass ratio of 0.005%:0.3%:0.5%:0.1%:0.05%, and the rest is water.

[0088] Example 2:

[0089] The preparation process is as in Example 1, and the composition ratio of each component in the preparation is toluene blue O, refined lignin, glucomannan, cysteine, sodium benzoate, with a mass ratio of 0.005%:0.3%:1.0%:0.1%:0.05%, and the rest is water.

[0090] Example 3:

[0091] The preparation process is as in Example 1, and the composition ratio of each component in the preparation is toluene blue O, refined lignin, glucomannan, cysteine, sodium benzoate, with a mass ratio of 0.005%:0.6%:0.5%:0.1%:0.05%, and the rest is water.

[0092] Example 4:

[0093] The preparation process is as in Example 1, and the composition ratio of each component in the preparation is toluene blue O, refined lignin, glucomannan, cysteine, sodium benzoate, with a mass ratio of 0.005%:0.6%:0.5%:0.1%:0.05%, and the rest is water.

[0094] Example 5:

[0095] The preparation process is as in Example 1, and the composition ratio of each component in the preparation is toluene blue O, refined lignin, glucomannan, cysteine, sodium benzoate, with a mass ratio of 0.005%:0.6%:0.5%:0.1%:0.05%, and the rest is water.

[0096] The performance and effect comparison of Comparative Example 1 to Example 5 is shown in Table 1:

[0097] Table 1 Performance and effect comparison

[0098] Stability test: each of the comparative examples and the examples obtained the preparation of 10 small samples, small samples with the same specification of 50 mL of transparent glass cylindrical sample bottle, placed in the natural environment of light storage, 1 month, 3 months, 6 months after the observation of the stability of the sample. If there is a surface conjunctival, flocculation, physical phase separation, viscosity reduction, etc. is not normal product. 10 small samples, the percentage of normal small sample is used to indicate the stability of the preparation.

[0099] Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor are within the scope of protection of the present application.

Claims

1. A process for preparing supramolecular carrier photosensitizers for photodynamic therapy, characterized in that: Step 1: Take a specified amount of distilled water, add a certain amount of glucomannan, and stir at room temperature until the glucomannan is completely swollen and dispersed. Set aside. Step 2: Take a specified amount of distilled water, add a certain amount of biomass refined lignin, and adjust the pH value to the range of 7.5 to 9.0 with baking soda while stirring at room temperature until completely dissolved to obtain a refined lignin solution for later use. Step 3: Take the specified amount of distilled water, fully dissolve the photosensitizer in the distilled water to prepare a photosensitizer aqueous solution of 200mg / L to 1000mg / L, then add a certain amount of cysteine, stir at room temperature until completely dissolved, and set aside. Step 4: Weigh a certain amount of sodium benzoate and add it to the specified amount of distilled water. Stir until the sodium benzoate is completely dissolved and set aside. Step 5: Mix the four solutions prepared above evenly, and add acetic acid to adjust the pH value to 6.0-6.5; Step 6: Place the sample in a water bath, heat to 45℃~65℃ and maintain the temperature for 5~48 hours, then allow it to cool naturally to obtain a supramolecular carrier-loaded photosensitizer formulation.

2. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 1, characterized in that, Refined lignin is prepared by alkali dissolution and acid precipitation. The acid precipitation process selects purified lignin separated within the pH range of 7.5 to 6.

5. The specific preparation process for refined lignin is as follows: Step 1: Disperse the raw material lignin in water, and while stirring, add sodium hydroxide solution to adjust the pH value to ≥11.0, and continue stirring until completely dissolved; the raw material lignin includes any one of the following: enzymatically hydrolyzed lignin, organic solvent lignin, ground wood lignin, alkali lignin, and sulfate lignin. Step 2: Filter to remove insoluble impurities; Step 3: While stirring, add sulfuric acid solution to the filtrate to adjust the pH to 7.

5. After stirring for a period of time, filter out the precipitated lignin and keep the filtrate for later use. Step 4: While stirring, slowly add dilute sulfuric acid solution to the collected filtrate to adjust the pH to 6.

5. Filter the solution, and repeatedly wash and dry the filtrate with distilled water to obtain the refined lignin.

3. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 1, characterized in that, The raw material lignin for the refined lignin includes any one of the following: enzymatically hydrolyzed lignin, organic solvent lignin, ground wood lignin, alkali lignin, and sulfate lignin.

4. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 1, characterized in that, The photosensitizer is at least one of silica sol gel-based toluidine blue O, toluidine blue, and methylene blue, and is formulated from the following components in the following mass percentages: 0.001-0.1% toluidine blue O, 2-15% nano silica, and the balance being physiological saline. Nano-silica includes hydrophilic silica and hydrophobic silica. The hydrophilicity and lipophilicity of the photosensitive compound can be controlled by adjusting the ratio of hydrophilic and hydrophobic silica.

5. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 4, characterized in that, The nano-silica includes fumed silica and liquid silica; The fumed silica is in an amorphous state, with an initial particle size between 7 and 40 nanometers. The liquid-phase silica has a porosity of 95%–99.8% and a specific surface area >1000 m². 2 / g; The liquid silica is produced by the sol-gel method, and the accompanying drying process adopts freeze drying or supercritical drying.

6. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 4, characterized in that, The preparation method includes the following steps: Step 1: Dissolve at least one of silica sol gel-based toluidine blue O, toluidine blue, and methylene blue in a specified amount of 85% sodium chloride physiological saline. Step 2: Using a high-speed disperser, slowly add the specified amount of nano-silica while stirring at a speed of 50-100 rpm. After adding all the silica, continue stirring for another 5 minutes. Step 3: Gradually adjust the speed to 3000-5000 rpm and continue stirring in the high-speed disperser for 10 minutes to ensure uniform dispersion; Step 4: Stop stirring, add the remaining 15% physiological saline while rinsing the inner wall of the container, and then stir at a low speed of 100 rpm for 10 minutes to obtain the photosensitizer.

7. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 6, characterized in that, It also includes a photosensitizer combination, the active ingredients of which include photosensitizer, sugar components and penetrant, in a mass percentage of 1:(10-200):(0-5); The photosensitizing combination agent uses physiological saline as a solvent, wherein the mass percentage of the active ingredient is 0.5% to 5%; The viscosity of the photosensitive compound is 5 to 5000 mPa·s.

8. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 7, characterized in that, The preparation method of photosensitizer combination includes the following steps: Step 1: Dissolve the photosensitizer thoroughly in sodium chloride saline solution; Step 2: Add the sugar components; dissolve or swell, and stir to mix thoroughly; Step 3: Add the penetrant; mix thoroughly under stirring. Step 4: Add physiological saline to the total mass percentage of 100%, and stir thoroughly to obtain the final mixture.

9. The preparation process of the supramolecular carrier photosensitizer for photodynamic therapy according to claim 8, characterized in that, When the combination agent is applied to root canal photodynamic anti-inflammatory and sterilization treatment, it is a low-viscosity preparation; the viscosity is between 3 and 100 mPa·s, including 3 mPa·s and 100 mPa·s; and more preferably, the viscosity is between 5 and 10 mPa·s. When the combination agent is applied to the photodynamic anti-inflammatory and sterilization treatment of periodontal pockets, it is a medium viscosity formulation; the viscosity is in the range of 100 to 1800 mPa·s, including 1800 mPa·s; and more preferably, the viscosity is 500 to 1000 mPa·s. When the combination agent is applied to the photodynamic anti-inflammatory and sterilization treatment of the gingival surface, it is a high-viscosity preparation; the viscosity is in the range of 1800 to 5000 mPa·s, including 5000 mPa·s; and more preferably the viscosity is 2500 to 3000 mPa·s.

10. A supramolecular carrier formulation, using the preparation process described in any one of claims 1 to 7, characterized in that: It is composed of refined lignin, glucomannan, cysteine, and sodium benzoate in a mass ratio of 0.1–1.0% : 0.5–3% : 0.1–0.5% : 0.05–0.2%, with the balance being water.

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